Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
Department of Radiology, University of São Paulo Medical School, São Paulo, Brazil.
Neuropathol Appl Neurobiol. 2018 Apr;44(3):286-297. doi: 10.1111/nan.12430. Epub 2017 Sep 20.
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.
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.
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.
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.
对认知正常的老年人群中，转活性应答 DNA 结合蛋白 43（TDP-43）蛋白病的流行率进行系统回顾和荟萃分析。
我们系统地回顾了认知正常的老年人群中 TDP-43 蛋白病的流行率，并使用 Mini-Mental State Examination 或临床痴呆评定量表进行了评估。我们使用随机效应模型估计了 TDP-43 蛋白病的总体流行率，并根据年龄、性别、样本量、研究质量、用于评估 TDP-43 聚集物的抗体、分析的脑区、Braak 分期、阿尔茨海默病协会注册中心评分、海马硬化和地理位置进行了分层。
系统回顾共确定了 505 篇文章，7 篇文章纳入荟萃分析，共纳入 1196 名认知正常的老年人群。我们发现 TDP-43 蛋白病的总体流行率为 24%。TDP-43 蛋白病的流行率在地理位置上差异很大（北美：37%，亚洲：29%，欧洲：14%，拉丁美洲：11%）。根据研究质量（质量评分>7：22% vs. 质量评分<7：42%）、用于评估 TDP-43 蛋白病的抗体（天然：18% vs. 磷酸化：24%）以及海马硬化的存在（无海马硬化：24% vs. 有海马硬化：48%），TDP-43 蛋白病的估计流行率也有所不同。按年龄、性别、分析脑区、样本量和 AD 神经病理学严重程度进行的其他分层分析显示，TDP-43 的汇总流行率相似。
不同的方法来评估 TDP-43，以及不同人群的生活方式和遗传因素的差异可能解释了我们的结果。需要标准化 TDP-43 的测量，并开展关于遗传和生活方式特征对神经退行性疾病发展影响的未来研究。
