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Meta-Analysis
. 2018 Apr;44(3):286-297.
doi: 10.1111/nan.12430. Epub 2017 Sep 20.

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

C Nascimento  1 , A T Di Lorenzo Alho  2   3 , C Bazan Conceição Amaral  4 , R E P Leite  5 , R Nitrini  6 , W Jacob-Filho  5 , C A Pasqualucci  4 , S R K Hokkanen  7 , S Hunter  7 , H Keage  8 , G G Kovacs  9 , L T Grinberg  4   10 , C K Suemoto  5
Affiliations
Meta-Analysis

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

C Nascimento et al. Neuropathol Appl Neurobiol. 2018 Apr.

Abstract

Objective: To 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.

Methods: We 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.

Results: A 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.

Conclusions: Different 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.

Keywords: post mortem; TDP-43 proteinopathy; brain ageing; dementia; elderly.

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Figures

Figure 1
Figure 1
Flow diagram of the literature search and study selection through the different phases of the systematic review.
Figure 2
Figure 2
Estimated prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy of the included articles and overall meta-analysis pooled prevalence
Figure 3
Figure 3
Estimated prevalence values of transactive response DNA-binding protein 43 proteinopathy of the included articles grouped by geographic location (all brain regions, A vs. only limbic brain regions, B).
Figure 4
Figure 4
Publication bias assessed by the funnel plot of the logit prevalence of transactive response DNA-binding protein 43 (TDP- 43) proteinopathy plotted against the standard error
See this image and copyright information in PMC

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