Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis

Author(s):Show less -

Nascimento, C. ^[1] ; Di Lorenzo Alho, A. T. ^{[2, 3]} ; Bazan Conceicao Amaral, C. ^[4] ; Leite, R. E. P. ^[5] ; Nitrini, R. ^[6] ; Jacob-Filho, W. ^[5] ; Pasqualucci, C. A. ^[4] ; Hokkanen, S. R. K. ^[7] ; Hunter, S. ^[7] ; Keage, H. ^[8] ; Kovacs, G. G. ^[9] ; Grinberg, L. T. ^{[4, 10]} ; Suemoto, C. K. ^[5]

Affiliation

^[1] Univ Sao Paulo, Med Sch, Dept Psychiat, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Dept Radiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Hosp lsraelita Albert Einstein, Med Sch, Inst Cerebro, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Med Sch, Dept Pathol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Med Sch, Div Geriatr, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Med Sch, Dept Neurol, Sao Paulo - Brazil

^[7] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge - England

^[8] Univ South Australia, Sch Psychol, Social Work & Social Policy, Adelaide, SA - Australia

^[9] Med Univ Vienna, Inst Neurol, Vienna - Austria

^[10] Univ San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94117 - USA

• Document type: Review article
• Source: NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY; v. 44, n. 3, p. 286-297, APR 2018.
• Web of Science Citations: 10

Abstract

ObjectiveTo perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. MethodsWe systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. ResultsA total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. ConclusionsDifferent methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed. (AU)

• FAPESP's process: 11/19833-7 - Characterization of TDP-43 changes during normal aging: a postmortem study
• Grantee: Camila Nascimento Mantelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/17365-7 - Unraveling the molecular basis of abnormal TDP-43 deposition: focusing on therapeutic approaches
• Grantee: Camila Nascimento Mantelli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral