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Мисфолдинг белков в патогенезе и диагностике нейродегенеративных заболеваний (обзор)

Мисфолдинг белков в патогенезе и диагностике нейродегенеративных заболеваний (обзор)

П.П. Трегуб, Н.А. Колотьева, П.А. Чекулаев, А.А. Грошков, С.Н. Иллариошкин, А.Б. Салмина, М.А. Пирадов
Ключевые слова: нейродегенеративные заболевания; белковая амплификация; биомаркеры; мисфолдинг; болезнь Альцгеймера; болезнь Паркинсона.
2025, том 17, номер 4, стр. 60.
DOI: https://doi.org/10.17691/stm2025.17.4.06

Полный текст статьи

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В обзоре выполнена систематизация имеющихся сведений о мисфолдинге белков в патогенезе нейродегенеративных заболеваний (с акцентом на α-синуклеине, β-амилоиде и тау-белке). Рассматриваются современные лабораторные и нейровизуализационные методы, применяемые для клинической диагностики и научных исследований протеинопатий. В работе приводится описание перспективных методик белковой амплификации, позволяющих обнаруживать сверхнизкие концентрации аберрантных форм белков в биологических жидкостях организма. Рассматриваются также проблемы и перспективы ранней диагностики нейродегенеративных заболеваний путем детекции мисфолдинга белков.

  1. Agnello L., Ciaccio M. Neurodegenerative diseases: from molecular basis to therapy. Int J Mol Sci 2022; 23(21): 12854, https://doi.org/10.3390/ijms232112854.
  2. Feigin V.L., Vos T., Nichols E., Owolabi M.O., Carroll W.M., Dichgans M., Deuschl G., Parmar P., Brainin M., Murray C. The global burden of neurological disorders: translating evidence into policy. Lancet Neurol 2020; 19(3): 255–265, https://doi.org/10.1016/S1474-4422(19)30411-9.
  3. Jan A., Gokce O., Luthi-Carter R., Lashuel H.A. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. J Biol Chem 2008; 283(42): 28176–28189, https://doi.org/10.1074/jbc.M803159200.
  4. Zhang Y., Wu K.M., Yang L., Dong Q., Yu J.T. Tauopathies: new perspectives and challenges. Mol Neurodegener 2022; 17(1): 28, https://doi.org/10.1186/s13024-022-00533-z.
  5. Bordbar S., Alijanzadeh D., Samieefar N., Khazeei Tabari M.A., Pourbakhtyaran E., Rezaei N. The role of alpha-synuclein in neurodevelopmental diseases. Mol Neurobiol 2025; 62(1): 962–972, https://doi.org/10.1007/s12035-024-04305-2.
  6. Sharma R., Khan Z., Mehan S., Das Gupta G., Narula A.S. Unraveling the multifaceted insights into amyotrophic lateral sclerosis: genetic underpinnings, pathogenesis, and therapeutic horizons. Mutat Res Rev Mutat Res 2024; 794: 108518, https://doi.org/10.1016/j.mrrev.2024.108518.
  7. Calabrese G., Molzahn C., Mayor T. Protein interaction networks in neurodegenerative diseases: from physiological function to aggregation. J Biol Chem 2022; 298(7): 102062, https://doi.org/10.1016/j.jbc.2022.102062.
  8. Li B., Chen M., Zhu C. Neuroinflammation in prion disease. Int J Mol Sci 2021; 22(4): 2196, https://doi.org/10.3390/ijms22042196.
  9. Pérez-Millan A., Thirion B., Falgàs N., Borrego-Écija S., Bosch B., Juncà-Parella J., Tort-Merino A., Sarto J., Augé J.M., Antonell A., Bargalló N., Balasa M., Lladó A., Sánchez-Valle R., Sala-Llonch R. Beyond group classification: probabilistic differential diagnosis of frontotemporal dementia and Alzheimer’s disease with MRI and CSF biomarkers. Neurobiol Aging 2024; 144: 1–11, https://doi.org/10.1016/j.neurobiolaging.2024.08.008.
  10. Erkkinen M.G., Kim M.O., Geschwind M.D. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol 2018; 10(4): a033118, https://doi.org/10.1101/cshperspect.a033118.
  11. Magalhães P., Lashuel H.A. Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies. NPJ Parkinsons Dis 2022; 8(1): 93, https://doi.org/10.1038/s41531-022-00357-0.
  12. Jia J., Ning Y., Chen M., Wang S., Yang H., Li F., Ding J., Li Y., Zhao B., Lyu J., Yang S., Yan X., Wang Y., Qin W., Wang Q., Li Y., Zhang J., Liang F., Liao Z., Wang S. Biomarker changes during 20 years preceding Alzheimer’s disease. N Engl J Med 2024; 390(8): 712–722, https://doi.org/10.1056/NEJMoa2310168.
  13. Tatarnikova O.G., Orlov M.A., Bobkova N.V. Beta-amyloid and tau-protein: structure, interaction, and prion-like properties. Biochemistry (Mosc) 2015; 80(13): 1800–1819, https://doi.org/10.1134/S000629791513012X.
  14. Arber C., Lovejoy C., Harris L., Willumsen N., Alatza A., Casey J.M., Lines G., Kerins C., Mueller A.K., Zetterberg H., Hardy J., Ryan N.S., Fox N.C., Lashley T., Wray S. Familial Alzheimer’s disease mutations in PSEN1 lead to premature human stem cell neurogenesis. Cell Rep 2021; 34(2): 108615, https://doi.org/10.1016/j.celrep.2020.108615.
  15. Li Y., Schindler S.E., Bollinger J.G., Ovod V., Mawuenyega K.G., Weiner M.W., Shaw L.M., Masters C.L., Fowler C.J., Trojanowski J.Q., Korecka M., Martins R.N., Janelidze S., Hansson O., Bateman R.J. Validation of plasma amyloid-β 42/40 for detecting Alzheimer disease amyloid plaques. Neurology 2022; 98(7): e688–e699, https://doi.org/10.1212/WNL.0000000000013211.
  16. Yu H., Wu J. Amyloid-β: a double agent in Alzheimer’s disease? Biomed Pharmacother 2021; 139: 111575, https://doi.org/10.1016/j.biopha.2021.111575.
  17. Sulatskaya A.I., Rychkov G.N., Sulatsky M.I., Mikhailova E.V., Melnikova N.M., Andozhskaya V.S., Kuznetsova I.M., Turoverov K.K. New evidence on a distinction between Aβ40 and Aβ42 amyloids: thioflavin t binding modes, clustering tendency, degradation resistance, and cross-seeding. Int J Mol Sci 2022; 23(10): 5513, https://doi.org/10.3390/ijms23105513.
  18. Braun G.A., Dear A.J., Sanagavarapu K., Zetterberg H., Linse S. Amyloid-β peptide 37, 38 and 40 individually and cooperatively inhibit amyloid-β 42 aggregation. Chem Sci 2022; 13(8): 2423–2439, https://doi.org/10.1039/d1sc02990h.
  19. Goedert M., Eisenberg D.S., Crowther R.A. Propagation of tau aggregates and neurodegeneration. Annu Rev Neurosci 2017; 40: 189–210, https://doi.org/10.1146/annurev-neuro-072116-031153.
  20. Hu J., Sha W., Yuan S., Wu J., Huang Y. Aggregation, transmission, and toxicity of the microtubule-associated protein tau: a complex comprehension. Int J Mol Sci 2023; 24(19): 15023, https://doi.org/10.3390/ijms241915023.
  21. Alonso A.D.C., El Idrissi A., Candia R., Morozova V., Kleiman F.E. Tau: more than a microtubule-binding protein in neurons. Cytoskeleton (Hoboken) 2024; 81(1): 71–77, https://doi.org/10.1002/cm.21795.
  22. Boyarko B., Hook V. Human Tau isoforms and proteolysis for production of toxic tau fragments in neurodegeneration. Front Neurosci 2021; 15: 702788, https://doi.org/10.3389/fnins.2021.702788.
  23. Rösler T.W., Tayaranian Marvian A., Brendel M., Nykänen N.P., Höllerhage M., Schwarz S.C., Hopfner F., Koeglsperger T., Respondek G., Schweyer K., Levin J., Villemagne V.L., Barthel H., Sabri O., Müller U., Meissner W.G., Kovacs G.G., Höglinger G.U. Four-repeat tauopathies. Prog Neurobiol 2019; 180: 101644, https://doi.org/10.1016/j.pneurobio.2019.101644.
  24. Chaudhry A., Houlden H., Rizig M. Novel fluid biomarkers to differentiate frontotemporal dementia and dementia with Lewy bodies from Alzheimer’s disease: a systematic review. J Neurol Sci 2020; 415: 116886, https://doi.org/10.1016/j.jns.2020.116886.
  25. Barthélemy N.R., Liu H., Lu W., Kotzbauer P.T., Bateman R.J., Lucey B.P. Sleep deprivation affects tau phosphorylation in human cerebrospinal fluid. Ann Neurol 2020; 87(5): 700–709, https://doi.org/10.1002/ana.25702.
  26. Leuzy A., Janelidze S., Mattsson-Carlgren N., Palmqvist S., Jacobs D., Cicognola C., Stomrud E., Vanmechelen E., Dage J.L., Hansson O. Comparing the clinical utility and diagnostic performance of CSF P-Tau181, P-Tau217, and P-Tau231 assays. Neurology 2021; 97(17): e1681–e1694, https://doi.org/10.1212/WNL.0000000000012727.
  27. Therriault J., Vermeiren M., Servaes S., Tissot C., Ashton N.J., Benedet A.L., Karikari T.K., Lantero-Rodriguez J., Brum W.S., Lussier F.Z., Bezgin G., Stevenson J., Rahmouni N., Kunach P., Wang Y.T., Fernandez-Arias J., Socualaya K.Q., Macedo A.C., Ferrari-Souza J.P., Ferreira P.C.L., Bellaver B., Leffa D.T., Zimmer E.R., Vitali P., Soucy J.P., Triana-Baltzer G., Kolb H.C., Pascoal T.A., Saha-Chaudhuri P., Gauthier S., Zetterberg H., Blennow K., Rosa-Neto P. Association of phosphorylated tau biomarkers with amyloid positron emission tomography vs tau positron emission tomography. JAMA Neurol 2023; 80(2): 188–199, https://doi.org/10.1001/jamaneurol.2022.4485.
  28. Carnazza K.E., Komer L.E., Xie Y.X., Pineda A., Briano J.A., Gao V., Na Y., Ramlall T., Buchman V.L., Eliezer D., Sharma M., Burré J. Synaptic vesicle binding of α-synuclein is modulated by β- and γ-synucleins. Cell Rep 2022; 39(2): 110675, https://doi.org/10.1016/j.celrep.2022.110675.
  29. Calabresi P., Mechelli A., Natale G., Volpicelli-Daley L., Di Lazzaro G., Ghiglieri V. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis 2023; 14(3): 176, https://doi.org/10.1038/s41419-023-05672-9.
  30. Yang Y., Shi Y., Schweighauser M., Zhang X., Kotecha A., Murzin A.G., Garringer H.J., Cullinane P.W., Saito Y., Foroud T., Warner T.T., Hasegawa K., Vidal R., Murayama S., Revesz T., Ghetti B., Hasegawa M., Lashley T., Scheres S.H.W., Goedert M. Structures of α-synuclein filaments from human brains with Lewy pathology. Nature 2022; 610(7933): 791–795, https://doi.org/10.1038/s41586-022-05319-3.
  31. Estaun-Panzano J., Arotcarena M.L., Bezard E. Monitoring α-synuclein aggregation. Neurobiol Dis 2023; 176: 105966, https://doi.org/10.1016/j.nbd.2022.105966.
  32. Dovidchenko N.V., Leonova E.I., Galzitskaya O.V. Mechanisms of amyloid fibril formation. Biochemistry (Mosc) 2014; 79(13): 1515–1527, https://doi.org/10.1134/S0006297914130057.
  33. Kachkin D.V., Volkov K.V., Sopova J.V., Bobylev A.G., Fedotov S.A., Inge-Vechtomov S.G., Galzitskaya O.V., Chernoff Y.O., Rubel A.A., Aksenova A.Y. Human RAD51 protein forms amyloid-like aggregates in vitro. Int J Mol Sci 2022; 23(19): 11657, https://doi.org/10.3390/ijms231911657.
  34. Fitzpatrick A.W., Debelouchina G.T., Bayro M.J., Clare D.K., Caporini M.A., Bajaj V.S., Jaroniec C.P., Wang L., Ladizhansky V., Müller S.A., MacPhee C.E., Waudby C.A., Mott H.R., De Simone A., Knowles T.P., Saibil H.R., Vendruscolo M., Orlova E.V., Griffin R.G., Dobson C.M. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proc Natl Acad Sci U S A 2013; 110(14): 5468–5473, https://doi.org/10.1073/pnas.1219476110.
  35. Min J.H., Sarlus H., Oasa S., Harris R.A. Thioflavin-T: application as a neuronal body and nucleolar stain and the blue light photo enhancement effect. Sci Rep 2024; 14(1): 24846, https://doi.org/10.1038/s41598-024-74359-8.
  36. Goldy J.N., Youker R.T. Characterization of spatial differences in two misfolded proteins during aggresome formation. MicroPubl Biol 2024, https://doi.org/10.17912/micropub.biology.001312.
  37. Kaur G., Poljak A., Braidy N., Crawford J.D., Lo J., Sachdev P.S. Fluid biomarkers and APOE status of early onset Alzheimer’s disease variants: a systematic review and meta-analysis. J Alzheimers Dis 2020; 75(3): 827–843, https://doi.org/10.3233/JAD-200052.
  38. Belloy M.E., Andrews S.J., Le Guen Y., Cuccaro M., Farrer L.A., Napolioni V., Greicius M.D. APOE genotype and Alzheimer disease risk across age, sex, and population ancestry. JAMA Neurol 2023; 80(12): 1284–1294, https://doi.org/10.1001/jamaneurol.2023.3599.
  39. Madore C., Yin Z., Leibowitz J., Butovsky O. Microglia, lifestyle stress, and neurodegeneration. Immunity 2020; 52(2): 222–240, https://doi.org/10.1016/j.immuni.2019.12.003.
  40. Bantle C.M., Phillips A.T., Smeyne R.J., Rocha S.M., Olson K.E., Tjalkens R.B. Infection with mosquito-borne alphavirus induces selective loss of dopaminergic neurons, neuroinflammation and widespread protein aggregation. NPJ Parkinsons Dis 2019; 5: 20, https://doi.org/10.1038/s41531-019-0090-8.
  41. Han X., Sun S., Sun Y., Song Q., Zhu J., Song N., Chen M., Sun T., Xia M., Ding J., Lu M., Yao H., Hu G. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. Autophagy 2019; 15(11): 1860–1881, https://doi.org/10.1080/15548627.2019.1596481.
  42. Won S.J., Fong R., Butler N., Sanchez J., Zhang Y., Wong C., Tambou Nzoutchoum O., Huynh A., Pan J., Swanson R.A. Neuronal oxidative stress promotes α-synuclein aggregation in vivo. Antioxidants (Basel) 2022; 11(12): 2466, https://doi.org/10.3390/antiox11122466.
  43. Wegmann S., Biernat J., Mandelkow E. A current view on tau protein phosphorylation in Alzheimer’s disease. Curr Opin Neurobiol 2021; 69: 131–138, https://doi.org/10.1016/j.conb.2021.03.003.
  44. Conway K.A., Lee S.J., Rochet J.C., Ding T.T., Williamson R.E., Lansbury P.T. Jr. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc Natl Acad Sci U S A 2000; 97(2): 571–576, https://doi.org/10.1073/pnas.97.2.571.
  45. Sgarbossa A. Natural biomolecules and protein aggregation: emerging strategies against amyloidogenesis. Int J Mol Sci 2012; 13(12): 17121–17137, https://doi.org/10.3390/ijms131217121.
  46. Harsolia R.S., Kanwar A., Gour S., Kumar V., Kumar V., Bansal R., Kumar S., Singh M., Yadav J.K. Predicted aggregation-prone region (APR) in βB1-crystallin forms the amyloid-like structure and induces aggregation of soluble proteins isolated from human cataractous eye lens. Int J Biol Macromol 2020; 163: 702–710, https://doi.org/10.1016/j.ijbiomac.2020.07.028.
  47. Housmans J.A.J., Wu G., Schymkowitz J., Rousseau F. A guide to studying protein aggregation. FEBS J 2023; 290(3): 554–583, https://doi.org/10.1111/febs.16312.
  48. Braak H., Del Tredici K., Rüb U., de Vos R.A., Jansen Steur E.N., Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24(2): 197–211, https://doi.org/10.1016/s0197-4580(02)00065-9.
  49. Horsager J., Knudsen K., Sommerauer M. Clinical and imaging evidence of brain-first and body-first Parkinson’s disease. Neurobiol Dis 2022; 164: 105626, https://doi.org/10.1016/j.nbd.2022.105626.
  50. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82(4): 239–259, https://doi.org/10.1007/BF00308809.
  51. Trejo-Lopez J.A., Yachnis A.T., Prokop S. Neuropathology of Alzheimer’s disease. Neurotherapeutics 2022; 19(1): 173–185, https://doi.org/10.1007/s13311-021-01146-y.
  52. Macedo A.C., Tissot C., Therriault J., Servaes S., Wang Y.T., Fernandez-Arias J., Rahmouni N., Lussier F.Z., Vermeiren M., Bezgin G., Vitali P., Ng K.P., Zimmer E.R., Guiot M.C., Pascoal T.A., Gauthier S., Rosa-Neto P. The use of tau PET to stage Alzheimer disease according to the braak staging framework. J Nucl Med 2023; 64(8): 1171–1178, https://doi.org/10.2967/jnumed.122.265200.
  53. Leng K., Li E., Eser R., Piergies A., Sit R., Tan M., Neff N., Li S.H., Rodriguez R.D., Suemoto C.K., Leite R.E.P., Ehrenberg A.J., Pasqualucci C.A., Seeley W.W., Spina S., Heinsen H., Grinberg L.T., Kampmann M. Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease. Nat Neurosci 2021; 24(2): 276–287, https://doi.org/10.1038/s41593-020-00764-7.
  54. Yang S., Park J.H., Lu H.C. Axonal energy metabolism, and the effects in aging and neurodegenerative diseases. Mol Neurodegener 2023; 18(1): 49, https://doi.org/10.1186/s13024-023-00634-3.
  55. Zimmer T.S., Orr A.L., Orr A.G. Astrocytes in selective vulnerability to neurodegenerative disease. Trends Neurosci 2024; 47(4): 289–302, https://doi.org/10.1016/j.tins.2024.02.008.
  56. Ma J., Gao J., Wang J., Xie A. Prion-like mechanisms in Parkinson’s disease. Front Neurosci 2019; 13: 552, https://doi.org/10.3389/fnins.2019.00552.
  57. da Silva Correia A., Schmitz M., Fischer A.L., da Silva Correia S., Simonetti F.L., Saher G., Goya-Maldonado R., Arora A.S., Fischer A., Outeiro T.F., Zerr I. Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo. Alzheimers Dement 2024; 20(10): 6776–6792, https://doi.org/10.1002/alz.14120.
  58. Renner M., Melki R. Protein aggregation and prionopathies. Pathol Biol (Paris) 2014; 62(3): 162–168, https://doi.org/10.1016/j.patbio.2014.01.003.
  59. Condello C., Westaway D., Prusiner S.B. Expanding the prion paradigm to include Alzheimer and Parkinson diseases. JAMA Neurol 2024; 81(10): 1023–1024, https://doi.org/10.1001/jamaneurol.2024.2464.
  60. Aulić S., Masperone L., Narkiewicz J., Isopi E., Bistaffa E., Ambrosetti E., Pastore B., De Cecco E., Scaini D., Zago P., Moda F., Tagliavini F., Legname G. α-Synuclein amyloids hijack prion protein to gain cell entry, facilitate cell-to-cell spreading and block prion replication. Sci Rep 2017; 7(1): 10050, https://doi.org/10.1038/s41598-017-10236-x.
  61. Brás I.C., Lopes L.V., Outeiro T.F. Sensing α-synuclein from the outside via the prion protein: implications for neurodegeneration. Mov Disord 2018; 33(11): 1675–1684, https://doi.org/10.1002/mds.27478.
  62. Clavaguera F., Hench J., Goedert M., Tolnay M. Invited review: prion-like transmission and spreading of tau pathology. Neuropathol Appl Neurobiol 2015; 41(1): 47–58, https://doi.org/10.1111/nan.12197.
  63. Volpicelli-Daley L.A., Luk K.C., Lee V.M. Addition of exogenous α-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous α-synuclein to Lewy body and Lewy neurite-like aggregates. Nat Protoc 2014; 9(9): 2135–2146, https://doi.org/10.1038/nprot.2014.143.
  64. Tarutani A., Suzuki G., Shimozawa A., Nonaka T., Akiyama H., Hisanaga S., Hasegawa M. The effect of fragmented pathogenic α-synuclein seeds on prion-like propagation. J Biol Chem 2016; 291(36): 18675–18688, https://doi.org/10.1074/jbc.M116.734707.
  65. Novotny R., Langer F., Mahler J., Skodras A., Vlachos A., Wegenast-Braun B.M., Kaeser S.A., Neher J.J., Eisele Y.S., Pietrowski M.J., Nilsson K.P., Deller T., Staufenbiel M., Heimrich B., Jucker M. Conversion of synthetic Aβ to in vivo active seeds and amyloid plaque formation in a hippocampal slice culture model. J Neurosci 2016; 36(18): 5084–5093, https://doi.org/10.1523/JNEUROSCI.0258-16.2016.
  66. Kane M.D., Lipinski W.J., Callahan M.J., Bian F., Durham R.A., Schwarz R.D., Roher A.E., Walker L.C. Evidence for seeding of beta-amyloid by intracerebral infusion of Alzheimer brain extracts in beta-amyloid precursor protein-transgenic mice. J Neurosci 2000; 20(10): 3606–3611, https://doi.org/10.1523/JNEUROSCI.20-10-03606.2000.
  67. Eisele Y.S., Bolmont T., Heikenwalder M., Langer F., Jacobson L.H., Yan Z.X., Roth K., Aguzzi A., Staufenbiel M., Walker L.C., Jucker M. Induction of cerebral beta-amyloidosis: intracerebral versus systemic Abeta inoculation. Proc Natl Acad Sci U S A 2009; 106(31): 12926–12931, https://doi.org/10.1073/pnas.0903200106.
  68. He Z., Guo J.L., McBride J.D., Narasimhan S., Kim H., Changolkar L., Zhang B., Gathagan R.J., Yue C., Dengler C., Stieber A., Nitla M., Coulter D.A., Abel T., Brunden K.R., Trojanowski J.Q., Lee V.M. Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 2018; 24(1): 29–38, https://doi.org/10.1038/nm.4443.
  69. Li X., Ospitalieri S., Robberechts T., Hofmann L., Schmid C., Rijal Upadhaya A., Koper M.J., von Arnim C.A.F., Kumar S., Willem M., Gnoth K., Ramakers M., Schymkowitz J., Rousseau F., Walter J., Ronisz A., Balakrishnan K., Thal D.R. Seeding, maturation and propagation of amyloid β-peptide aggregates in Alzheimer’s disease. Brain 2022; 145(10): 3558–3570, https://doi.org/10.1093/brain/awac202.
  70. Gary C., Lam S., Hérard A.S., Koch J.E., Petit F., Gipchtein P., Sawiak S.J., Caillierez R., Eddarkaoui S., Colin M., Aujard F., Deslys J.P.; French Neuropathology Network; Brouillet E., Buée L., Comoy E.E., Pifferi F., Picq J.L., Dhenain M. Encephalopathy induced by Alzheimer brain inoculation in a non-human primate. Acta Neuropathol Commun 2019; 7(1): 126, https://doi.org/10.1186/s40478-019-0771-x.
  71. Boi L., Pisanu A., Palmas M.F., Fusco G., Carboni E., Casu M.A., Satta V., Scherma M., Janda E., Mocci I., Mulas G., Ena A., Spiga S., Fadda P., De Simone A., Carta A.R. Modeling Parkinson’s disease neuropathology and symptoms by intranigral inoculation of preformed human α-synuclein oligomers. Int J Mol Sci 2020; 21(22): 8535, https://doi.org/10.3390/ijms21228535.
  72. Okuda S., Nakayama T., Uemura N., Hikawa R., Ikuno M., Yamakado H., Inoue H., Tachibana N., Hayashi Y., Takahashi R., Egawa N. Striatal-inoculation of α-synuclein preformed fibrils aggravated the phenotypes of REM sleep without atonia in A53T BAC-SNCA transgenic mice. Int J Mol Sci 2022; 23(21): 13390, https://doi.org/10.3390/ijms232113390.
  73. Flores-Cuadrado A., Saiz-Sanchez D., Mohedano-Moriano A., Martinez-Marcos A., Ubeda-Bañon I. Neurodegeneration and contralateral α-synuclein induction after intracerebral α-synuclein injections in the anterior olfactory nucleus of a Parkinson’s disease A53T mouse model. Acta Neuropathol Commun 2019; 7(1): 56, https://doi.org/10.1186/s40478-019-0713-7.
  74. Brackhan M., Calza G., Lundgren K., Bascuñana P., Brüning T., Soliymani R., Kumar R., Abelein A., Baumann M., Lalowski M., Pahnke J. Isotope-labeled amyloid-β does not transmit to the brain in a prion-like manner after peripheral administration. EMBO Rep 2022; 23(7): e54405, https://doi.org/10.15252/embr.202154405.
  75. Challis C., Hori A., Sampson T.R., Yoo B.B., Challis R.C., Hamilton A.M., Mazmanian S.K., Volpicelli-Daley L.A., Gradinaru V. Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice. Nat Neurosci 2020; 23(3): 327–336, https://doi.org/10.1038/s41593-020-0589-7.
  76. Ferrer I., Zelaya M.V., Aguiló García M., Carmona M., López-González I., Andrés-Benito P., Lidón L., Gavín R., Garcia-Esparcia P., Del Rio J.A. Relevance of host tau in tau seeding and spreading in tauopathies. Brain Pathol 2020; 30(2): 298–318, https://doi.org/10.1111/bpa.12778.
  77. Ferrer I., Andrés-Benito P., Garcia-Esparcia P., López-Gonzalez I., Valiente D., Jordán-Pirla M., Carmona M., Sala-Jarque J., Gil V., Del Rio J.A. Differences in tau seeding in newborn and adult wild-type mice. Int J Mol Sci 2022; 23(9): 4789, https://doi.org/10.3390/ijms23094789.
  78. Williams T., Sorrentino Z., Weinrich M., Giasson B.I., Chakrabarty P. Differential cross-seeding properties of tau and α-synuclein in mouse models of tauopathy and synucleinopathy. Brain Commun 2020; 2(2): fcaa090, https://doi.org/10.1093/braincomms/fcaa090.
  79. Pan L., Li C., Meng L., Tian Y., He M., Yuan X., Zhang G., Zhang Z., Xiong J., Chen G., Zhang Z. Tau accelerates α-synuclein aggregation and spreading in Parkinson’s disease. Brain 2022; 145(10): 3454–3471, https://doi.org/10.1093/brain/awac171.
  80. Bassil F., Brown H.J., Pattabhiraman S., Iwasyk J.E., Maghames C.M., Meymand E.S., Cox T.O., Riddle D.M., Zhang B., Trojanowski J.Q., Lee V.M. Amyloid-beta (Aβ) plaques promote seeding and spreading of alpha-synuclein and tau in a mouse model of Lewy body disorders with Aβ pathology. Neuron 2020; 105(2): 260–275.e6, https://doi.org/10.1016/j.neuron.2019.10.010.
  81. Hamaguchi T., Taniguchi Y., Sakai K., Kitamoto T., Takao M., Murayama S., Iwasaki Y., Yoshida M., Shimizu H., Kakita A., Takahashi H., Suzuki H., Naiki H., Sanjo N., Mizusawa H., Yamada M. Significant association of cadaveric dura mater grafting with subpial Aβ deposition and meningeal amyloid angiopathy. Acta Neuropathol 2016; 132(2): 313–315, https://doi.org/10.1007/s00401-016-1588-3.
  82. Peng C., Trojanowski J.Q., Lee V.M. Protein transmission in neurodegenerative disease. Nat Rev Neurol 2020; 16(4): 199–212, https://doi.org/10.1038/s41582-020-0333-7.
  83. Purro S.A., Farrow M.A., Linehan J., Nazari T., Thomas D.X., Chen Z., Mengel D., Saito T., Saido T., Rudge P., Brandner S., Walsh D.M., Collinge J. Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone. Nature 2018; 564(7736): 415–419, https://doi.org/10.1038/s41586-018-0790-y.
  84. Banerjee G., Farmer S.F., Hyare H., Jaunmuktane Z., Mead S., Ryan N.S., Schott J.M., Werring D.J., Rudge P., Collinge J. Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone. Nat Med 2024; 30(2): 394–402, https://doi.org/10.1038/s41591-023-02729-2.
  85. Tong M.K., Thakur A., Yang T., Wong S.K., Li W.K., Lee Y. Amyloid-β oligomer-induced neurotoxicity by exosomal interactions between neuron and microglia. Biochem Biophys Res Commun 2024; 727: 150312, https://doi.org/10.1016/j.bbrc.2024.150312.
  86. Ngolab J., Trinh I., Rockenstein E., Mante M., Florio J., Trejo M., Masliah D., Adame A., Masliah E., Rissman R.A. Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology. Acta Neuropathol Commun 2017; 5(1): 46, https://doi.org/10.1186/s40478-017-0445-5.
  87. Melachroinou K., Divolis G., Tsafaras G., Karampetsou M., Fortis S., Stratoulias Y., Papadopoulou G., Kriebardis A.G., Samiotaki M., Vekrellis K. Endogenous alpha-synuclein is essential for the transfer of pathology by exosome-enriched extracellular vesicles, following inoculation with preformed fibrils in vivo. Aging Dis 2024; 15(2): 869–892, https://doi.org/10.14336/AD.2023.0614.
  88. Guo M., Wang J., Zhao Y., Feng Y., Han S., Dong Q., Cui M., Tieu K. Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease. Brain 2020; 143(5): 1476–1497, https://doi.org/10.1093/brain/awaa090.
  89. Polanco J.C., Hand G.R., Briner A., Li C., Götz J. Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol. Acta Neuropathol 2021; 141(2): 235–256, https://doi.org/10.1007/s00401-020-02254-3.
  90. Jain N., Ulrich J.D. TREM2 and microglia exosomes: a potential highway for pathological tau. Mol Neurodegener 2022; 17(1): 73, https://doi.org/10.1186/s13024-022-00581-5.
  91. Sardar Sinha M., Ansell-Schultz A., Civitelli L., Hildesjö C., Larsson M., Lannfelt L., Ingelsson M., Hallbeck M. Alzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers. Acta Neuropathol 2018; 136(1): 41–56, https://doi.org/10.1007/s00401-018-1868-1.
  92. Ruan Z., Pathak D., Venkatesan Kalavai S., Yoshii-Kitahara A., Muraoka S., Bhatt N., Takamatsu-Yukawa K., Hu J., Wang Y., Hersh S., Ericsson M., Gorantla S., Gendelman H.E., Kayed R., Ikezu S., Luebke J.I., Ikezu T. Alzheimer’s disease brain-derived extracellular vesicles spread tau pathology in interneurons. Brain 2021; 144(1): 288–309, https://doi.org/10.1093/brain/awaa376.
  93. Wei S., Ma X., Chen Y., Wang J., Hu L., Liu Z., Mo L., Zhou N., Chen W., Zhu H., Yan S. Alzheimer’s disease-derived outer membrane vesicles exacerbate cognitive dysfunction, modulate the gut microbiome, and increase neuroinflammation and amyloid-β production. Mol Neurobiol 2025; 62(4): 5109–5132, https://doi.org/10.1007/s12035-024-04579-6.
  94. Liu W.L., Lin H.W., Lin M.R., Yu Y., Liu H.H., Dai Y.L., Chen L.W., Jia W.W., He X.J., Li X.L., Zhu J.F., Xue X.H., Tao J., Chen L.D. Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer’s disease: a meta-analysis and systematic review. Neural Regen Res 2022; 17(11): 2381–2390, https://doi.org/10.4103/1673-5374.335832.
  95. Kluge A., Bunk J., Schaeffer E., Drobny A., Xiang W., Knacke H., Bub S., Lückstädt W., Arnold P., Lucius R., Berg D., Zunke F. Detection of neuron-derived pathological α-synuclein in blood. Brain 2022; 145(9): 3058–3071, https://doi.org/10.1093/brain/awac115.
  96. Kluge A., Schaeffer E., Bunk J., Sommerauer M., Röttgen S., Schulte C., Roeben B., von Thaler A.-K., Welzel J., Lucius R., Heinzel S., Xiang W., Eschweiler G.W., Maetzler W., Suenkel U., Berg D. Detecting misfolded α-synuclein in blood years before the diagnosis of Parkinson’s disease. Mov Disord 2024; 39: 1289–1299, https://doi.org/10.1002/mds.29766.
  97. Mothes T., Portal B., Konstantinidis E., Eltom K., Libard S., Streubel-Gallasch L., Ingelsson M., Rostami J., Lindskog M., Erlandsson A. Astrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology. Acta Neuropathol Commun 2023; 11(1): 97, https://doi.org/10.1186/s40478-023-01589-8.
  98. Rajasekaran S., Witt S.N. Trojan horses and tunneling nanotubes enable α-synuclein pathology to spread in Parkinson disease. PLoS Biol 2021; 19(7): e3001331, https://doi.org/10.1371/journal.pbio.3001331.
  99. Scheiblich H., Eikens F., Wischhof L., Opitz S., Jüngling K., Cserép C., Schmidt S.V., Lambertz J., Bellande T., Pósfai B., Geck C., Spitzer J., Odainic A., Castro-Gomez S., Schwartz S., Boussaad I., Krüger R., Glaab E., Di Monte D.A., Bano D., Dénes Á., Latz E., Melki R., Pape H.C., Heneka M.T. Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes. Neuron 2024; 112(18): 3106–3125.e8, https://doi.org/10.1016/j.neuron.2024.06.029.
  100. Chakraborty R., Nonaka T., Hasegawa M., Zurzolo C. Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-synuclein and mitochondria. Cell Death Dis 2023; 14(5): 329, https://doi.org/10.1038/s41419-023-05835-8.
  101. Xu Y., Du S., Marsh J.A., Horie K., Sato C., Ballabio A., Karch C.M., Holtzman D.M., Zheng H. TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading. Mol Psychiatry 2021; 26(10): 5925–5939, https://doi.org/10.1038/s41380-020-0738-0.
  102. Shearer L.J., Petersen N.O., Woodside M.T. Internalization of α-synuclein oligomers into SH-SY5Y cells. Biophys J 2021; 120(5): 877–885, https://doi.org/10.1016/j.bpj.2020.12.031.
  103. Zhang S., Liu Y.Q., Jia C., Lim Y.J., Feng G., Xu E., Long H., Kimura Y., Tao Y., Zhao C., Wang C., Liu Z., Hu J.J., Ma M.R., Liu Z., Jiang L., Li D., Wang R., Dawson V.L., Dawson T.M., Li Y.M., Mao X., Liu C. Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson’s disease. Proc Natl Acad Sci U S A 2021; 118(26): e2011196118, https://doi.org/10.1073/pnas.2011196118.
  104. Shi J.M., Zhu L., Lan X., Zhao D.W., He Y.J., Sun Z.Q., Wu D., Li H.Y. Endocytosis is a key mode of interaction between extracellular β-amyloid and the cell membrane. Biophys J 2020; 119(6): 1078–1090, https://doi.org/10.1016/j.bpj.2020.07.035.
  105. Lungu O., Bares M. Editorial: neuropsychology through the MRI looking glass. Front Neurol 2020; 11: 609897, https://doi.org/10.3389/fneur.2020.609897.
  106. Bousiges O., Blanc F. Biomarkers of dementia with Lewy bodies: differential diagnostic with Alzheimer’s disease. Int J Mol Sci 2022; 23(12): 6371, https://doi.org/10.3390/ijms23126371.
  107. Smailagic N., Vacante M., Hyde C., Martin S., Ukoumunne O., Sachpekidis C. 18F-FDG PET for the early diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev 2015; 1(1): CD010632, https://doi.org/10.1002/14651858.CD010632.pub2.
  108. Lombardi G., Crescioli G., Cavedo E., Lucenteforte E., Casazza G., Bellatorre A.G., Lista C., Costantino G., Frisoni G., Virgili G., Filippini G. Structural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer’s disease in people with mild cognitive impairment. Cochrane Database Syst Rev 2020; 3(3): CD009628, https://doi.org/10.1002/14651858.CD009628.pub2.
  109. Solje E., Benussi A., Buratti E., Remes A.M., Haapasalo A., Borroni B. State-of-the-art methods and emerging fluid biomarkers in the diagnostics of dementia — a short review and diagnostic algorithm. Diagnostics (Basel) 2021; 11(5): 788, https://doi.org/10.3390/diagnostics11050788.
  110. Skillbäck T., Farahmand B.Y., Rosén C., Mattsson N., Nägga K., Kilander L., Religa D., Wimo A., Winblad B., Schott J.M., Blennow K., Eriksdotter M., Zetterberg H. Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia. Brain 2015; 138(Pt 9): 2716–2731, https://doi.org/10.1093/brain/awv181.
  111. Arranz J., Zhu N., Rubio-Guerra S., Rodríguez-Baz Í., Ferrer R., Carmona-Iragui M., Barroeta I., Illán-Gala I., Santos-Santos M., Fortea J., Lleó A., Tondo M., Alcolea D. Diagnostic performance of plasma pTau217, pTau181, Aβ1-42 and Aβ1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease. Alzheimers Res Ther 2024; 16(1): 139, https://doi.org/10.1186/s13195-024-01513-9.
  112. Gąsior-Głogowska M.E., Szulc N., Szefczyk M. Challenges in experimental methods. Methods Mol Biol 2022; 2340: 281–307, https://doi.org/10.1007/978-1-0716-1546-1_13.
  113. Guerrero-Ferreira R., Taylor N.M., Arteni A.A., Kumari P., Mona D., Ringler P., Britschgi M., Lauer M.E., Makky A., Verasdonck J., Riek R., Melki R., Meier B.H., Böckmann A., Bousset L., Stahlberg H. Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy. Elife 2019; 8: e48907, https://doi.org/10.7554/eLife.48907.
  114. Motta C., Di Donna M.G., Bonomi C.G., Assogna M., Chiaravalloti A., Mercuri N.B., Koch G., Martorana A. Different associations between amyloid-βeta 42, amyloid-βeta 40, and amyloid-βeta 42/40 with soluble phosphorylated-tau and disease burden in Alzheimer’s disease: a cerebrospinal fluid and fluorodeoxyglucose-positron emission tomography study. Alzheimers Res Ther 2023; 15(1): 144, https://doi.org/10.1186/s13195-023-01291-w.
  115. Santos J.R.F., Bauer C., Schuchhardt J., Wedekind D., Waniek K., Lachmann I., Wiltfang J., Vogelgsang J. Validation of a prototype tau Thr231 phosphorylation CSF ELISA as a potential biomarker for Alzheimer’s disease. J Neural Transm (Vienna) 2019; 126(3): 339–348, https://doi.org/10.1007/s00702-019-01982-5.
  116. Коваленко Е.А., Махнович Е.В., Первунина А.В., Акимов К.А., Мараховская Е.А., Боголепова А.Н. Био­мар­керы крови в ранней диагностике болезни Альцгеймера. Эффективная фармакотерапия 2023; 19(45): 30–36.
  117. Shinohara M., Hirokawa J., Shimodaira A., Tashiro Y., Suzuki K., Gheni G., Fukumori A., Matsubara T., Morishima M., Saito Y., Murayama S., Sato N. ELISA evaluation of tau accumulation in the brains of patients with Alzheimer disease. J Neuropathol Exp Neurol 2021; 80(7): 652–662, https://doi.org/10.1093/jnen/nlab047.
  118. Herrmann M., Golombowski S., Kräuchi K., Frey P., Mourton-Gilles C., Hulette C., Rosenberg C., Müller-Spahn F., Hock C. ELISA-quantitation of phosphorylated tau protein in the Alzheimer’s disease brain. Eur Neurol 1999; 42(4): 205–210, https://doi.org/10.1159/000008108.
  119. Teunissen C.E., Kimble L., Bayoumy S., Bolsewig K., Burtscher F., Coppens S., Das S., Gogishvili D., Fernandes Gomes B., Gómez de San José N., Mavrina E., Meda F.J., Mohaupt P., Mravinacová S., Waury K., Wojdała A.L., Abeln S., Chiasserini D., Hirtz C., Gaetani L., Vermunt L., Bellomo G., Halbgebauer S., Lehmann S., Månberg A., Nilsson P., Otto M., Vanmechelen E., Verberk I.M.W., Willemse E., Zetterberg H.; MIRIADE consortium. Methods to discover and validate biofluid-based biomarkers in neurodegenerative dementias. Mol Cell Proteomics 2023; 22(10): 100629, https://doi.org/10.1016/j.mcpro.2023.100629.
  120. Truffi M., Garofalo M., Ricciardi A., Cotta Ramusino M., Perini G., Scaranzin S., Gastaldi M., Albasini S., Costa A., Chiavetta V., Corsi F., Morasso C., Gagliardi S. Neurofilament-light chain quantification by Simoa and Ella in plasma from patients with dementia: a comparative study. Sci Rep 2023; 13(1): 4041, https://doi.org/10.1038/s41598-023-29704-8.
  121. Carrette O., Demalte I., Scherl A., Yalkinoglu O., Corthals G., Burkhard P., Hochstrasser D.F., Sanchez J.C. A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer’s disease. Proteomics 2003; 3(8): 1486–1494, https://doi.org/10.1002/pmic.200300470.
  122. Conrotto P., Souchelnytskyi S. Proteomic approaches in biological and medical sciences: principles and applications. Exp Oncol 2008; 30(3): 171–180.
  123. Bader J.M., Geyer P.E., Müller J.B., Strauss M.T., Koch M., Leypoldt F., Koertvelyessy P., Bittner D., Schipke C.G., Incesoy E.I., Peters O., Deigendesch N., Simons M., Jensen M.K., Zetterberg H., Mann M. Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer’s disease. Mol Syst Biol 2020; 16(6): e9356, https://doi.org/10.15252/msb.20199356.
  124. Karayel O., Virreira Winter S., Padmanabhan S., Kuras Y.I., Vu D.T., Tuncali I., Merchant K., Wills A.M., Scherzer C.R., Mann M. Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson’s disease. Cell Rep Med 2022; 3(6): 100661, https://doi.org/10.1016/j.xcrm.2022.100661.
  125. Teunissen C.E., Elias N., Koel-Simmelink M.J., Durieux-Lu S., Malekzadeh A., Pham T.V., Piersma S.R., Beccari T., Meeter L.H., Dopper E.G., van Swieten J.C., Jimenez C.R., Pijnenburg Y.A. Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics. Alzheimers Dement (Amst) 2016; 2: 86–94, https://doi.org/10.1016/j.dadm.2015.12.004.
  126. Laszlo Z.I., Hindley N., Sanchez Avila A., Kline R.A., Eaton S.L., Lamont D.J., Smith C., Spires-Jones T.L., Wishart T.M., Henstridge C.M. Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex. Acta Neuropathol Commun 2022; 10(1): 156, https://doi.org/10.1186/s40478-022-01455-z.
  127. Flynn J.D., Lee J.C. Raman fingerprints of amyloid structures. Chem Commun (Camb) 2018; 54(51): 6983–6986, https://doi.org/10.1039/c8cc03217c.
  128. Chen C., Qi J., Li Y., Li D., Wu L., Li R., Chen Q., Sun N. Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases. Front Neurosci 2024; 18: 1301107, https://doi.org/10.3389/fnins.2024.1301107.
  129. Lochocki B., Morrema T.H.J., Ariese F., Hoozemans J.J.M., de Boer J.F. The search for a unique Raman signature of amyloid-beta plaques in human brain tissue from Alzheimer’s disease patients. Analyst 2020; 145(5): 1724–1736, https://doi.org/10.1039/c9an02087j.
  130. Cennamo G., Montorio D., Morra V.B., Criscuolo C., Lanzillo R., Salvatore E., Camerlingo C., Lisitskiy M., Delfino I., Portaccio M., Lepore M. Surface-enhanced Raman spectroscopy of tears: toward a diagnostic tool for neurodegenerative disease identification. J Biomed Opt 2020; 25(8): 1–12, https://doi.org/10.1117/1.JBO.25.8.087002.
  131. Carlomagno C., Bertazioli D., Gualerzi A., Picciolini S., Andrico M., Rodà F., Meloni M., Banfi P.I., Verde F., Ticozzi N., Silani V., Messina E., Bedoni M. Identification of the raman salivary fingerprint of Parkinson’s disease through the spectroscopic-computational combinatory approach. Front Neurosci 2021; 15: 704963, https://doi.org/10.3389/fnins.2021.704963.
  132. Sun J., Shi Z., Wang L., Zhang X., Luo C., Hua J., Feng M., Chen Z., Wang M., Xu C. Construction of a microcavity-based microfluidic chip with simultaneous SERS quantification of dual biomarkers for early diagnosis of Alzheimer’s disease. Talanta 2023; 261: 124677, https://doi.org/10.1016/j.talanta.2023.124677.
  133. Soares Martins T., Magalhães S., Rosa I.M., Vogelgsang J., Wiltfang J., Delgadillo I., Catita J., da Cruz E Silva O.A.B., Nunes A., Henriques A.G. Potential of FTIR spectroscopy applied to exosomes for Alzheimer’s disease discrimination: a pilot study. J Alzheimers Dis 2020; 74(1): 391–405, https://doi.org/10.3233/JAD-191034.
  134. Soares Martins T., Ferreira M., Magalhães S., Leandro K., Almeida L.P., Vogelgsang J., Breitling B., Hansen N., Esselmann H., Wiltfang J., da Cruz E Silva O.A.B., Nunes A., Henriques A.G. FTIR spectroscopy and blood-derived extracellular vesicles duo in Alzheimer’s disease. J Alzheimers Dis 2024; 98(3): 1157–1167, https://doi.org/10.3233/JAD-231239.
  135. Paraskevaidi M., Morais C.L.M., Lima K.M.G., Snowden J.S., Saxon J.A., Richardson A.M.T., Jones M., Mann D.M.A., Allsop D., Martin-Hirsch P.L., Martin F.L. Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood. Proc Natl Acad Sci U S A 2017; 114(38): E7929–E7938, https://doi.org/10.1073/pnas.1701517114.
  136. Benseny-Cases N., Klementieva O., Cotte M., Ferrer I., Cladera J. Microspectroscopy (μFTIR) reveals co-localization of lipid oxidation and amyloid plaques in human Alzheimer disease brains. Anal Chem 2014; 86(24): 12047–12054, https://doi.org/10.1021/ac502667b.
  137. Palombo F., Tamagnini F., Jeynes J.C.G., Mattana S., Swift I., Nallala J., Hancock J., Brown J.T., Randall A.D., Stone N. Detection of Aβ plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry. Analyst 2018; 143(4): 850–857, https://doi.org/10.1039/c7an01747b.
  138. Röhr D., Boon B.D.C., Schuler M., Kremer K., Hoozemans J.J.M., Bouwman F.H., El-Mashtoly S.F., Nabers A., Großerueschkamp F., Rozemuller A.J.M., Gerwert K. Label-free vibrational imaging of different Aβ plaque types in Alzheimer’s disease reveals sequential events in plaque development. Acta Neuropathol Commun 2020; 8(1): 222, https://doi.org/10.1186/s40478-020-01091-5.
  139. Gras S.L., Waddington L.J., Goldie K.N. Transmission electron microscopy of amyloid fibrils. Methods Mol Biol 2011; 752: 197–214, https://doi.org/10.1007/978-1-60327-223-0_13.
  140. Kollmer M., Close W., Funk L., Rasmussen J., Bsoul A., Schierhorn A., Schmidt M., Sigurdson C.J., Jucker M., Fändrich M. Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue. Nat Commun 2019; 10(1): 4760, https://doi.org/10.1038/s41467-019-12683-8.
  141. Yang Y., Arseni D., Zhang W., Huang M., Lövestam S., Schweighauser M., Kotecha A., Murzin A.G., Peak-Chew S.Y., Macdonald J., Lavenir I., Garringer H.J., Gelpi E., Newell K.L., Kovacs G.G., Vidal R., Ghetti B., Ryskeldi-Falcon B., Scheres S.H.W., Goedert M. Cryo-EM structures of amyloid-β 42 filaments from human brains. Science 2022; 375(6577): 167–172, https://doi.org/10.1126/science.abm7285.
  142. Zhang H., Zheng X., Kwok R.T.K., Wang J., Leung N.L.C., Shi L., Sun J.Z., Tang Z., Lam J.W.Y., Qin A., Tang B.Z. In situ monitoring of molecular aggregation using circular dichroism. Nat Commun 2018; 9(1): 4961, https://doi.org/10.1038/s41467-018-07299-3.
  143. Waeytens J., Turbant F., Arluison V., Raussens V., Wien F. Analysis of bacterial amyloid interaction with lipidic membrane by orientated circular dichroism and infrared spectroscopies. Methods Mol Biol 2022; 2538: 217–234, https://doi.org/10.1007/978-1-0716-2529-3_15.
  144. Hu H.Y., Jiang L.L., Hong J.Y. Study of protein amyloid-like aggregates by solid-state circular dichroism spectroscopy. Curr Protein Pept Sci 2017; 18(1): 100–103, https://doi.org/10.2174/1389203717666160709185323.
  145. Rybicka A., Longhi G., Castiglioni E., Abbate S., Dzwolak W., Babenko V., Pecul M. Thioflavin T: electronic circular dichroism and circularly polarized luminescence induced by amyloid fibrils. Chemphyschem 2016; 17(18): 2931–2937, https://doi.org/10.1002/cphc.201600235.
  146. Protein folding, misfolding, and disease: methods and protocols. Hill A.F., Barnham K.J., Bottomley S.P., Cappai R. (editors). Humana Press; 2011, https://doi.org/10.1007/978-1-60327-223-0.
  147. Concha-Marambio L., Pritzkow S., Shahnawaz M., Farris C.M., Soto C. Seed amplification assay for the detection of pathologic alpha-synuclein aggregates in cerebrospinal fluid. Nat Protoc 2023; 18(4): 1179–1196, https://doi.org/10.1038/s41596-022-00787-3.
  148. Standke H.G., Kraus A. Seed amplification and RT-QuIC assays to investigate protein seed structures and strains. Cell Tissue Res 2023; 392(1): 323–335, https://doi.org/10.1007/s00441-022-03595-z.
  149. Saborio G.P., Permanne B., Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 2001; 411(6839): 810–813, https://doi.org/10.1038/35081095.
  150. Saá P., Castilla J., Soto C. Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 2006; 281(46): 35245–35252, https://doi.org/10.1074/jbc.M603964200.
  151. Wang F., Pritzkow S., Soto C. PMCA for ultrasensitive detection of prions and to study disease biology. Cell Tissue Res 2023; 392(1): 307–321, https://doi.org/10.1007/s00441-022-03727-5.
  152. Atarashi R., Wilham J.M., Christensen L., Hughson A.G., Moore R.A., Johnson L.M., Onwubiko H.A., Priola S.A., Caughey B. Simplified ultrasensitive prion detection by recombinant PrP conversion with shaking. Nat Methods 2008; 5(3): 211–212, https://doi.org/10.1038/nmeth0308-211.
  153. Atarashi R., Satoh K., Sano K., Fuse T., Yamaguchi N., Ishibashi D., Matsubara T., Nakagaki T., Yamanaka H., Shirabe S., Yamada M., Mizusawa H., Kitamoto T., Klug G., McGlade A., Collins S.J., Nishida N. Ultrasensitive human prion detection in cerebrospinal fluid by real-time quaking-induced conversion. Nat Med 2011; 17(2): 175–178, https://doi.org/10.1038/nm.2294.
  154. Giaccone G., Moda F. PMCA applications for prion detection in peripheral tissues of patients with variant Creutzfeldt–Jakob disease. Biomolecules 2020; 10(3): 405, https://doi.org/10.3390/biom10030405.
  155. Rhoads D.D., Wrona A., Foutz A., Blevins J., Glisic K., Person M., Maddox R.A., Belay E.D., Schonberger L.B., Tatsuoka C., Cohen M.L., Appleby B.S. Diagnosis of prion diseases by RT-QuIC results in improved surveillance. Neurology 2020; 95(8): e1017–e1026, https://doi.org/10.1212/WNL.0000000000010086.
  156. Brandel J.P., Culeux A., Grznarova K., Levavasseur E., Lamy P., Privat N., Welaratne A., Denouel A., Laplanche J.L., Haik S. Amplification techniques and diagnosis of prion diseases. Rev Neurol (Paris) 2019; 175(7–8): 458–463, https://doi.org/10.1016/j.neurol.2019.06.002.
  157. Groveman B.R., Orrù C.D., Hughson A.G., Raymond L.D., Zanusso G., Ghetti B., Campbell K.J., Safar J., Galasko D., Caughey B. Rapid and ultra-sensitive quantitation of disease-associated α-synuclein seeds in brain and cerebrospinal fluid by αSyn RT-QuIC. Acta Neuropathol Commun 2018; 6(1): 7, https://doi.org/10.1186/s40478-018-0508-2.
  158. Shahnawaz M., Mukherjee A., Pritzkow S., Mendez N., Rabadia P., Liu X., Hu B., Schmeichel A., Singer W., Wu G., Tsai A.L., Shirani H., Nilsson K.P.R., Low P.A., Soto C. Discriminating α-synuclein strains in Parkinson’s disease and multiple system atrophy. Nature 2020; 578(7794): 273–277, https://doi.org/10.1038/s41586-020-1984-7.
  159. Bellomo G., De Luca C.M.G., Paoletti F.P., Gaetani L., Moda F., Parnetti L. α-Synuclein seed amplification assays for diagnosing synucleinopathies: the way forward. Neurology 2022; 99(5): 195–205, https://doi.org/10.1212/WNL.0000000000200878.
  160. Okuzumi A., Hatano T., Matsumoto G., Nojiri S., Ueno S.I., Imamichi-Tatano Y., Kimura H., Kakuta S., Kondo A., Fukuhara T., Li Y., Funayama M., Saiki S., Taniguchi D., Tsunemi T., McIntyre D., Gérardy J.J., Mittelbronn M., Kruger R., Uchiyama Y., Nukina N., Hattori N. Propagative α-synuclein seeds as serum biomarkers for synucleinopathies. Nat Med 2023; 29(6): 1448–1455, https://doi.org/10.1038/s41591-023-02358-9.
  161. Manca M., Kraus A. Defining the protein seeds of neurodegeneration using real-time quaking-induced conversion assays. Biomolecules 2020; 10(9): 1233, https://doi.org/10.3390/biom10091233.
  162. Fairfoul G., McGuire L.I., Pal S., Ironside J.W., Neumann J., Christie S., Joachim C., Esiri M., Evetts S.G., Rolinski M., Baig F., Ruffmann C., Wade-Martins R., Hu M.T., Parkkinen L., Green A.J. Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol 2016; 3(10): 812–818, https://doi.org/10.1002/acn3.338.
  163. Rossi M., Candelise N., Baiardi S., Capellari S., Giannini G., Orrù C.D., Antelmi E., Mammana A., Hughson A.G., Calandra-Buonaura G., Ladogana A., Plazzi G., Cortelli P., Caughey B., Parchi P. Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies. Acta Neuropathol 2020; 140(1): 49–62, https://doi.org/10.1007/s00401-020-02160-8.
  164. Wang Y., Hu J., Chen X., Wang S., Zhang C., Hu J., Guo D., Liu X. Real-time quaking-induced conversion assay is accurate for Lewy body diseases: a meta-analysis. Neurol Sci 2022; 43(7): 4125–4132, https://doi.org/10.1007/s10072-022-06014-x.
  165. Srivastava A., Alam P., Caughey B. RT-QuIC and related assays for detecting and quantifying prion-like pathological seeds of α-synuclein. Biomolecules 2022; 12(4): 576, https://doi.org/10.3390/biom12040576.
  166. Grossauer A., Hemicker G., Krismer F., Peball M., Djamshidian A., Poewe W., Seppi K., Heim B. α-Synuclein seed amplification assays in the diagnosis of synucleinopathies using cerebrospinal fluid-a systematic review and meta-analysis. Mov Disord Clin Pract 2023; 10(5): 737–747, https://doi.org/10.1002/mdc3.13710.
  167. Brockmann K., Quadalti C., Lerche S., Rossi M., Wurster I., Baiardi S., Roeben B., Mammana A., Zimmermann M., Hauser A.K., Deuschle C., Schulte C., Waniek K., Lachmann I., Sjödin S., Brinkmalm A., Blennow K., Zetterberg H., Gasser T., Parchi P. Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol Commun 2021; 9(1): 175, https://doi.org/10.1186/s40478-021-01276-6.
  168. Siderowf A., Concha-Marambio L., Lafontant D.E., Farris C.M., Ma Y., Urenia P.A., Nguyen H., Alcalay R.N., Chahine L.M., Foroud T., Galasko D., Kieburtz K., Merchant K., Mollenhauer B., Poston K.L., Seibyl J., Simuni T., Tanner C.M., Weintraub D., Videnovic A., Choi S.H., Kurth R., Caspell-Garcia C., Coffey C.S., Frasier M., Oliveira L.M.A., Hutten S.J., Sherer T., Marek K., Soto C. Parkinson’s Progression Markers Initiative. Assessment of heterogeneity among participants in the Parkinson’s progression markers initiative cohort using α-synuclein seed amplification: a cross-sectional study. Lancet Neurol 2023; 22(5): 407–417, https://doi.org/10.1016/S1474-4422(23)00109-6.
  169. Bongianni M., Catalan M., Perra D., Fontana E., Janes F., Bertolotti C., Sacchetto L., Capaldi S., Tagliapietra M., Polverino P., Tommasini V., Bellavita G., Kachoie E.A., Baruca R., Bernardini A., Valente M., Fiorini M., Bronzato E., Tamburin S., Bertolasi L., Brozzetti L., Cecchini M.P., Gigli G., Monaco S., Manganotti P., Zanusso G. Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease. Transl Neurodegener 2022; 11(1): 37, https://doi.org/10.1186/s40035-022-00311-3.
  170. Perra D., Bongianni M., Novi G., Janes F., Bessi V., Capaldi S., Sacchetto L., Tagliapietra M., Schenone G., Morbelli S., Fiorini M., Cattaruzza T., Mazzon G., Orrù C.D., Catalan M., Polverino P., Bernardini A., Pellitteri G., Valente M., Bertolotti C., Nacmias B., Maggiore G., Cavallaro T., Manganotti P., Gigli G., Monaco S., Nobili F., Zanusso G. Alpha-synuclein seeds in olfactory mucosa and cerebrospinal fluid of patients with dementia with Lewy bodies. Brain Commun 2021; 3(2): fcab045, https://doi.org/10.1093/braincomms/fcab045.
  171. Bargar C., Wang W., Gunzler S.A., LeFevre A., Wang Z., Lerner A.J., Singh N., Tatsuoka C., Appleby B., Zhu X., Xu R., Haroutunian V., Zou W.Q., Ma J., Chen S.G. Streamlined alpha-synuclein RT-QuIC assay for various biospecimens in Parkinson’s disease and dementia with Lewy bodies. Acta Neuropathol Commun 2021; 9(1): 62, https://doi.org/10.1186/s40478-021-01175-w.
  172. Stefani A., Iranzo A., Holzknecht E., Perra D., Bongianni M., Gaig C., Heim B., Serradell M., Sacchetto L., Garrido A., Capaldi S., Sánchez-Gómez A., Cecchini M.P., Mariotto S., Ferrari S., Fiorini M., Schmutzhard J., Cocchiara P., Vilaseca I., Brozzetti L., Monaco S., Jose Marti M., Seppi K., Tolosa E., Santamaria J., Högl B., Poewe W., Zanusso G; SINBAR (Sleep Innsbruck Barcelona) group. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain 2021; 144(4): 1118–1126, https://doi.org/10.1093/brain/awab005.
  173. Kuang Y., Mao H., Gan T., Guo W., Dai W., Huang W., Wu Z., Li H., Huang X., Yang X., Xu P.Y. A skin-specific α-synuclein seeding amplification assay for diagnosing Parkinson’s disease. NPJ Parkinsons Dis 2024; 10(1): 129, https://doi.org/10.1038/s41531-024-00738-7.
  174. Wang Z., Gilliland T., Kim H.J., Gerasimenko M., Sajewski K., Camacho M.V., Bebek G., Chen S.G., Gunzler S.A., Kong Q. A minimally invasive biomarker for sensitive and accurate diagnosis of Parkinson’s disease. Acta Neuropathol Commun 2024; 12(1): 167, https://doi.org/10.1186/s40478-024-01873-1.
  175. Manca M., Standke H.G., Browne D.F., Huntley M.L., Thomas O.R., Orrú C.D., Hughson A.G., Kim Y., Zhang J., Tatsuoka C., Zhu X., Hiniker A., Coughlin D.G., Galasko D., Kraus A. Tau seeds occur before earliest Alzheimer’s changes and are prevalent across neurodegenerative diseases. Acta Neuropathol 2023; 146(1): 31–50, https://doi.org/10.1007/s00401-023-02574-0.
  176. Saijo E., Ghetti B., Zanusso G., Oblak A., Furman J.L., Diamond M.I., Kraus A., Caughey B. Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid. Acta Neuropathol 2017; 133(5): 751–765, https://doi.org/10.1007/s00401-017-1692-z.
  177. Saijo E., Metrick M.A. 2nd, Koga S., Parchi P., Litvan I., Spina S., Boxer A., Rojas J.C., Galasko D., Kraus A., Rossi M., Newell K., Zanusso G., Grinberg L.T., Seeley W.W., Ghetti B., Dickson D.W., Caughey B. 4-repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration. Acta Neuropathol 2020; 139(1): 63–77, https://doi.org/10.1007/s00401-019-02080-2.
  178. Kraus A., Saijo E., Metrick M.A. 2nd, Newell K., Sigurdson C.J., Zanusso G., Ghetti B., Caughey B. Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease. Acta Neuropathol 2019; 137(4): 585–598, https://doi.org/10.1007/s00401-018-1947-3.
  179. Tennant J.M., Henderson D.M., Wisniewski T.M., Hoover E.A. RT-QuIC detection of tauopathies using full-length tau substrates. Prion 2020; 14(1): 249–256, https://doi.org/10.1080/19336896.2020.1832946.
  180. Salvadores N., Shahnawaz M., Scarpini E., Tagliavini F., Soto C. Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer’s disease. Cell Rep 2014; 7(1): 261–268, https://doi.org/10.1016/j.celrep.2014.02.031.
  181. Estrada L.D., Chamorro D., Yañez M.J., Gonzalez M., Leal N., von Bernhardi R., Dulcey A.E., Marugan J., Ferrer M., Soto C., Zanlungo S., Inestrosa N.C., Alvarez A.R. Reduction of blood amyloid-β oligomers in Alzheimer’s disease transgenic mice by c-Abl kinase inhibition. J Alzheimers Dis 2016; 54(3): 1193–1205, https://doi.org/10.3233/JAD-151087.
  182. An S.S., Lim K.T., Oh H.J., Lee B.S., Zukic E., Ju Y.R., Yokoyama T., Kim S.Y., Welker E. Differentiating blood samples from scrapie infected and non-infected hamsters by detecting disease-associated prion proteins using Multimer Detection System. Biochem Biophys Res Commun 2010; 392(4): 505–509, https://doi.org/10.1016/j.bbrc.2010.01.053.
  183. An S.S.A., Lee B.S., Yu J.S., Lim K., Kim G.J., Lee R., Kim S., Kang S., Park Y.H., Wang M.J., Yang Y.S., Youn Y.C., Kim S. Dynamic changes of oligomeric amyloid β levels in plasma induced by spiked synthetic Aβ42. Alzheimers Res Ther 2017; 9(1): 86, https://doi.org/10.1186/s13195-017-0310-6.
  184. Meyer N., Janot J.M., Torrent J., Balme S. Real-time fast amyloid seeding and translocation of α-synuclein with a nanopipette. ACS Cent Sci 2022; 8(4): 441–448, https://doi.org/10.1021/acscentsci.1c01404.
  185. Meyer N., Bentin J., Janot J.M., Abrao-Nemeir I., Charles-Achille S., Pratlong M., Aquilina A., Trinquet E., Perrier V., Picaud F., Torrent J., Balme S. Ultrasensitive detection of Aβ42 seeds in cerebrospinal fluid with a nanopipette-based real-time fast amyloid seeding and translocation assay. Anal Chem 2023; 95(34): 12623–12630, https://doi.org/10.1021/acs.analchem.3c00017.
  186. Christenson P.R., Li M., Rowden G., Larsen P.A., Oh S.H. Nanoparticle-enhanced RT-QuIC (Nano-QuIC) diagnostic assay for misfolded proteins. Nano Lett 2023; 23(9): 4074–4081, https://doi.org/10.1021/acs.nanolett.3c01001.
  187. Kim Y., Ko S.M., Nam J.M. Protein-nanoparticle interaction-induced changes in protein structure and aggregation. Chem Asian J 2016; 11(13): 1869–1877, https://doi.org/10.1002/asia.201600236.
  188. Hajipour M.J., Safavi-Sohi R., Sharifi S., Mahmoud N., Ashkarran A.A., Voke E., Serpooshan V., Ramezankhani M., Milani A.S., Landry M.P., Mahmoudi M. An overview of nanoparticle protein corona literature. Small 2023; 19(36): e2301838, https://doi.org/10.1002/smll.202301838.
  189. Chatzikonstantinou S., Kazis D., Karantali E., Knights M., McKenna J., Petridis F., Mavroudis I. A meta-analysis on RT-QuIC for the diagnosis of sporadic CJD. Acta Neurol Belg 2021; 121(2): 341–349, https://doi.org/10.1007/s13760-021-01596-3.
  190. Krawczuk D., Groblewska M., Mroczko J., Winkel I., Mroczko B. The role of α-synuclein in etiology of neurodegenerative diseases. Int J Mol Sci 2024; 25(17): 9197, https://doi.org/10.3390/ijms25179197.
  191. Zhang K., Mizuma H., Zhang X., Takahashi K., Jin C., Song F., Gao Y., Kanayama Y., Wu Y., Li Y., Ma L., Tian M., Zhang H., Watanabe Y. PET imaging of neural activity, β-amyloid, and tau in normal brain aging. Eur J Nucl Med Mol Imaging 2021; 48(12): 3859–3871, https://doi.org/10.1007/s00259-021-05230-5.
  192. Park M.C., Kim M., Lim G.T., Kang S.M., An S.S., Kim T.S., Kang J.Y. Droplet-based magnetic bead immunoassay using microchannel-connected multiwell plates (μCHAMPs) for the detection of amyloid beta oligomers. Lab Chip 2016; 16(12): 2245–2253, https://doi.org/10.1039/c6lc00013d.
  193. Cheong D.Y., Lee W., Park I., Park J., Lee G. Amyloid formation in nanoliter droplets. Int J Mol Sci 2022; 23(10): 5480, https://doi.org/10.3390/ijms23105480.
  194. Pfammatter M., Andreasen M., Meisl G., Taylor C.G., Adamcik J., Bolisetty S., Sánchez-Ferrer A., Klenerman D., Dobson C.M., Mezzenga R., Knowles T.P.J., Aguzzi A., Hornemann S. Absolute quantification of amyloid propagons by digital microfluidics. Anal Chem 2017; 89(22): 12306–12313, https://doi.org/10.1021/acs.analchem.7b03279.
Tregub P.P., Kolotyeva N.A., Chekulayev P.A., Groshkov A.A., Illarioshkin S.N., Salmina A.B., Piradov M.A. Protein Misfolding in the Pathogenesis and Diagnosis of Neurodegenerative Diseases (Review). Sovremennye tehnologii v medicine 2025; 17(4): 60, https://doi.org/10.17691/stm2025.17.4.06


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