Progressos recentes em p-tau como um biomarcador de doença de Alzheimer baseado no sangue
DOI:
https://doi.org/10.34024/rnc.2021.v29.12512Palavras-chave:
Doença de Alzheimer, biomarcadores, sangue, plasma, p-tau, tauResumo
Introdução. A hipótese da cascata amiloide propõe que as placas senis extracelulares - em grande parte compostas por peptídeos beta-amiloide (Aβ) agregados - são responsáveis pelos eventos que levam à morte neuronal que ocorre na doença de Alzheimer (DA). Por outro lado, a proteína tau hiperfosforilada (p-tau) e desestruturada é responsável pelos emaranhados neurofibrilares intracelulares, também comuns na DA. Os critérios de diagnóstico clínico para DA incluem testes dos biomarcadores Aβ e p-tau no líquido cefalorraquidiano (LCR), além de medidas de neuroimagem, história clínica e testes psicométricos. No entanto, devido à sua natureza invasiva, efeitos colaterais e necessidade de pessoal treinado em ambiente hospitalar para sua coleta, os biomarcadores do LCR não são adequados para triagem em larga escala. Portanto, biomarcadores alternativos baseados no sangue estão sob intensa investigação. Objetivos. Enfocar os avanços recentes em diferentes isoformas de p-tau como biomarcadores para DA baseados no sangue. Método. Revisão realizada por buscas nas bases de dados Medline/PubMed. Resultados. As isoformas 181 e 217 da p-tau representam moléculas acessíveis e escaláveis para triagem e diagnóstico de DA, principalmente devido à sua capacidade de diferenciar pacientes com a doença de participantes cognitivamente saudáveis. Esses resultados devem ser reproduzidos em coortes maiores e mais representativas da diversidade populacional. Conclusões. Essa revisão fornece uma exploração mais abrangente de p-tau sanguínea como um biomarcador molecular específico para DA, o que poderia contribuir não apenas para a triagem de pacientes pré-sintomáticos para ensaios clínicos, mas também para monitorar a progressão da doença e avaliar terapias modificadoras da doença.
Downloads
Métricas
Referências
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112-7. https://doi.org/10.1016/S0140-6736(05)67889-0
Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer Report 2018: the state of the art of dementia research: new frontiers. London: Alzheimer’s Disease International; 2018. https://www.alzint.org/u/WorldAlzheimerReport2018.pdf
Wada-Isoe K, Kikuchi T, Umeda-Kameyama Y, Mori T, Akishita M, Nakamura Y, et al. ABC Dementia Scale Classifies Alzheimer's Disease Patients into Subgroups Characterized by Activities of Daily Living, Behavioral and Psychological Symptoms of Dementia, and Cognitive Function. J Alzheimers Dis 2020;73:383-92. https://doi.org/10.3233/JAD-190767
Liu PP, Xie Y, Meng XY, Kang JS. History and progress of hypotheses and clinical trials for Alzheimer's disease. Signal Transduct Target Ther 2019;4:29. https://doi.org/10.1038/s41392-019-0063-8
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256:184-5. https://doi.org/10.1126/science.1566067
Maccioni RB, Farias G, Morales I, Navarrete L. The revitalized tau hypothesis on Alzheimer's disease. Arch Med Res 2010;41:226-31. https://doi.org/10.1016/j.arcmed.2010.03.007
Kametani F, Hasegawa M. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease. Front Neurosci 2018;12:25. https://doi.org/10.3389/fnins.2018.00025
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002;297:353-6. https://doi.org/10.1126/science.1072994
Barbier P, Zejneli O, Martinho M, Lasorsa A, Belle V, Smet-Nocca C, et al. Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects. Front Aging Neurosci 2019;11:204. https://doi.org/10.3389/fnagi.2019.00204
Merezhko M, Uronen RL, Huttunen HJ. The Cell Biology of Tau Secretion. Front Mol Neurosci 2020;13:569818. https://doi.org/10.3389/fnmol.2020.569818
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-44. https://doi.org/10.1212/wnl.34.7.939
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr., Kawas CH, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:263-9. https://doi.org/10.1016/j.jalz.2011.03.005
Mattsson-Carlgren N, Palmqvist S, Blennow K, Hansson O. Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies. Nat Commun 2020;11:6252. https://doi.org/10.1038/s41467-020-19957-6
Rosen C, Hansson O, Blennow K, Zetterberg H. Fluid biomarkers in Alzheimer's disease - current concepts. Mol Neurodegenerat 2013;8:20. https://doi.org/10.1186/1750-1326-8-20
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harbor Perspect Biol 2015;7:a020412. https://doi.org/10.1101/cshperspect.a020412
Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol 2016;15:673-84. https://doi.org/10.1016/S1474-4422(16)00070-3
Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, Chiotis K, et al. Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers. Lancet Neurol 2017;16:661-76. https://doi.org/10.1016/S1474-4422(17)30159-X
Wright BL, Lai JT, Sinclair AJ. Cerebrospinal fluid and lumbar puncture: a practical review. J Neurol 2012;259:1530-45. https://doi.org/10.1007/s00415-012-6413-x
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009;302:385-93. https://doi.org/10.1001/jama.2009.1064
Chetelat G, Arbizu J, Barthel H, Garibotto V, Law I, Morbelli S, et al. Amyloid-PET and (18)F-FDG-PET in the diagnostic investigation of Alzheimer's disease and other dementias. Lancet Neurol 2020;19:951-62. https://doi.org/10.1016/S1474-4422(20)30314-8
Ossenkoppele R, Rabinovici GD, Smith R, Cho H, Scholl M, Strandberg O, et al. Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 2018;320:1151-62. https://doi.org/10.1001/jama.2018.12917
Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer's disease. Trends Pharmacol Sci 2015;36:297-309. https://doi.org/10.1016/j.tips.2015.03.002
Zhang S, Han D, Tan X, Feng J, Guo Y, Ding Y. Diagnostic accuracy of 18 F-FDG and 11 C-PIB-PET for prediction of short-term conversion to Alzheimer's disease in subjects with mild cognitive impairment. Int J Clin Pract 2012;66:185-98. https://doi.org/10.1111/j.1742-1241.2011.02845.x
Ewers M, Mattsson N, Minthon L, Molinuevo JL, Antonell A, Popp J, et al. CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study. Alzheimers Dement 2015;11:1306-15. https://doi.org/10.1016/j.jalz.2014.12.006
Nadebaum DP, Krishnadas N, Poon AM, Kalff V, Lichtenstein M, Villemagne VL, et al. A head-to-head comparison of cerebral blood flow SPECT and (18) F-FDG PET in the diagnosis of Alzheimer's Disease. Intern Med J 2020:1-23. https://doi.org/10.1111/imj.14890
Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 2012;11:669-78. https://doi.org/10.1016/S1474-4422(12)70142-4
Hampel H, O'Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S, et al. Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic. Nat Rev Neurol 2018;14:639-52. https://doi.org/10.1038/s41582-018-0079-7
De Meyer S, Schaeverbeke JM, Verberk IMW, Gille B, De Schaepdryver M, Luckett ES, et al. Comparison of ELISA- and SIMOA-based quantification of plasma Abeta ratios for early detection of cerebral amyloidosis. Alzheimers Res Ther 2020;12:162. https://doi.org/10.1186/s13195-020-00728-w
Derisbourg M, Leghay C, Chiappetta G, Fernandez-Gomez FJ, Laurent C, Demeyer D, et al. Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms. Scientific Rep 2015;5:9659. https://doi.org/10.1038/srep09659
Arendt T, Stieler JT, Holzer M. Tau and tauopathies. Brain Res Bull 2016;126:238-92. https://doi.org/10.1016/j.brainresbull.2016.08.018
Guo T, Noble W, Hanger DP. Roles of tau protein in health and disease. Acta Neuropathol 2017;133:665-704. https://doi.org/10.1007/s00401-017-1707-9
Iqbal K, Liu F, Gong CX, Grundke-Iqbal I. Tau in Alzheimer disease and related tauopathies. Curr Alzheimer Res 2010;7:656-64. https://doi.org/10.2174/156720510793611592
Iqbal K, Liu F, Gong CX. Tau and neurodegenerative disease: the story so far. Nature reviews Neurology 2016;12:15-27. https://doi.org/10.1038/nrneurol.2015.225
Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW. A protein factor essential for microtubule assembly. Proceed Nat Acad Sci USA 1975;72:1858-62. https://doi.org/10.1073/pnas.72.5.1858
Kosik KS, Joachim CL, Selkoe DJ. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proceed Nat Acad Sci USA 1986;83:4044-8. https://doi.org/10.1073/pnas.83.11.4044
Mehta PD, Thal L, Wisniewski HM, Grundke-Iqbal I, Iqbal K. Paired helical filament antigen in CSF. Lancet 1985;2:35. https://doi.org/10.1016/s0140-6736(85)90074-1
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239-59. https://doi.org/10.1007/BF00308809
Goedert M, Spillantini MG, Potier MC, Ulrich J, Crowther RA. Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. Embo J 1989;8:393-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC400819/pdf/emboj00126-0065.pdf
Zilka N, Filipcik P, Koson P, Fialova L, Skrabana R, Zilkova M, et al. Truncated tau from sporadic Alzheimer's disease suffices to drive neurofibrillary degeneration in vivo. FEBS Lett 2006;580:3582-8. https://doi.org/10.1016/j.febslet.2006.05.029
Khatoon S, Grundke-Iqbal I, Iqbal K. Brain levels of microtubule-associated protein tau are elevated in Alzheimer's disease: a radioimmuno-slot-blot assay for nanograms of the protein. J Neurochem 1992;59:750-3. https://doi.org/10.1111/j.1471-4159.1992.tb09432.x
Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs 2010;24:375-98. https://doi.org/10.2165/11533100-000000000-00000
Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, et al. Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 1993;61:1828-34. https://doi.org/10.1111/j.1471-4159.1993.tb09823.x
Aschenbrenner AJ, Gordon BA, Benzinger TLS, Morris JC, Hassenstab JJ. Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease. Neurology 2018;91:e859-66. https://doi.org/10.1212/WNL.0000000000006075
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010;6:131-44. https://doi.org/10.1038/nrneurol.2010.4
Schindler SE, Li Y, Todd KW, Herries EM, Henson RL, Gray JD, et al. Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease. Alzheimers Dement 2019;15:655-65. https://doi.org/10.1016/j.jalz.2018.12.019
Ferreira D, Rivero-Santana A, Perestelo-Perez L, Westman E, Wahlund LO, Sarria A, et al. Improving CSF Biomarkers' Performance for Predicting Progression from Mild Cognitive Impairment to Alzheimer's Disease by Considering Different Confounding Factors: A Meta-Analysis. Front Aging Neurosci 2014;6:287. https://doi.org/10.3389/fnagi.2014.00287
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 2012;367:795-804. https://doi.org/10.1056/NEJMoa1202753
Suarez-Calvet M, Karikari TK, Ashton NJ, Lantero Rodriguez J, Mila-Aloma M, Gispert JD, et al. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Abeta pathology are detected. EMBO Mol Med 2020;12:e12921. https://doi.org/10.15252/emmm.202012921
Shen XN, Li JQ, Wang HF, Li HQ, Huang YY, Yang YX, et al. Plasma amyloid, tau, and neurodegeneration biomarker profiles predict Alzheimer's disease pathology and clinical progression in older adults without dementia. Alzheimers Dement (Amst) 2020;12:e12104. https://doi.org/10.1002/dad2.12104
Fossati S, Ramos Cejudo J, Debure L, Pirraglia E, Sone JY, Li Y, et al. Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer's disease. Alzheimers Dement (Amst) 2019;11:483-92. https://doi.org/10.1016/j.dadm.2019.05.001
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 2020;19:422-33. https://doi.org/10.1016/S1474-4422(20)30071-5
Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, et al. Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimers Dement 2018;14:989-97. https://doi.org/10.1016/j.jalz.2018.02.013
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodriguez J, Snellman A, et al. Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease. JAMA Neurol 2021;78:396-406. https://doi.org/10.1001/jamaneurol.2020.4986
Janelidze S, Berron D, Smith R, Strandberg O, Proctor NK, Dage JL, et al. Associations of Plasma Phospho-Tau217 Levels With Tau Positron Emission Tomography in Early Alzheimer Disease. JAMA Neurol 2020;78:149-56. https://doi.org/10.1001/jamaneurol.2020.4201
Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, et al. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA 2020;324:772-81. https://doi.org/10.1001/jama.2020.12134
Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, et al. Longitudinal plasma p-tau217 is increased in early stages of Alzheimer's disease. Brain J Neurol 2020;143:3234-41. https://doi.org/10.1093/brain/awaa286
Rizzi L, Maria Portal M, Batista CEA, Missiaggia L, Roriz-Cruz M. CSF Abeta1-42, but not p-Tau181, differentiates aMCI from SCI. Brain Res 2018;1678:27-31. https://doi.org/10.1016/j.brainres.2017.10.008
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2021 Danyelle Sadala, Vyctoria Ramos, Danielle dos Santos Maia Salheb de Oliveira, Maria José da Silva Fernandes, Marcia Regina Cominetti
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Publicado: 2021-08-05