TDP-43 病理学与阿尔茨海默病谱中 18F-Florbetapir PET 信号的整体和区域性关联。

Association of TDP-43 Pathology with Global and Regional 18F-Florbetapir PET Signal in the Alzheimer's Disease Spectrum.

机构信息

German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.

Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.

出版信息

J Alzheimers Dis. 2021;79(2):663-670. doi: 10.3233/JAD-201032.

DOI:10.3233/JAD-201032

PMID:33337372

Abstract

BACKGROUND

TAR DNA-binding protein 43 (TDP-43) has been recognized as a frequent co-pathology of Alzheimer's disease (AD). The effect of the presence of TDP-43 pathology on in vivo measures of AD-related amyloid pathology using amyloid sensitive PET is still unresolved.

OBJECTIVE

To study the association of TDP-43 pathology with antemortem amyloid PET signal.

METHODS

We studied 30 cases from the ADNI autopsy sample with available ratings of presence of TDP-43 and antemortem amyloid sensitive 18F-FlorbetapirPET. We used Bayesian regression to determine the effect of TDP-43 on global and regional amyloid PET signal. In a post-hoc analysis, we assessed the association of TDP-43 pathology with antemortem memory performance.

RESULTS

We found substantial to strong evidence for a negative effect of TDP-43 (Bayes factor against the null model (BF10) = 9.0) and hippocampal sclerosis (BF10 = 6.4) on partial volume corrected hippocampal 18F-Florbetapir uptake. This effect was only partly mediated by the negative effect of TDP-43 on hippocampal volume. In contrast, Bayesian regression supported that there is no effect of TDP-43 on global cortical PET-signal (BF10 = 0.65). We found an anecdotal level of evidence for a negative effect of TDP-43 pathology on antemortem memory performance after accounting for global amyloid PET signal (BF10 = 1.6).

CONCLUSION

Presence of TDP-43 pathology does not confound the global amyloid PET-signal but has a selective effect on hippocampal PET-signal that appears only partially dependent on TDP-43 mediated atrophy.

摘要

背景

TAR DNA 结合蛋白 43（TDP-43）已被认为是阿尔茨海默病（AD）的常见共病。使用淀粉样蛋白敏感 PET 测量 AD 相关淀粉样蛋白病理学的体内测量中，TDP-43 病理学的存在的影响仍未解决。

目的

研究 TDP-43 病理学与生前淀粉样蛋白 PET 信号的关联。

方法

我们研究了 ADNI 尸检样本中的 30 例病例，这些病例均有 TDP-43 和生前淀粉样蛋白敏感 18F-Florbetapir PET 的存在评分。我们使用贝叶斯回归来确定 TDP-43 对全局和区域淀粉样蛋白 PET 信号的影响。在事后分析中，我们评估了 TDP-43 病理学与生前记忆表现的关联。

结果

我们发现 TDP-43（反对零模型的贝叶斯因子（BF10）=9.0）和海马硬化（BF10=6.4）对部分体积校正的海马 18F-Florbetapir 摄取有实质性到很强的负效应。这种影响仅部分由 TDP-43 对海马体积的负效应介导。相比之下，贝叶斯回归支持 TDP-43 对全局皮质 PET 信号没有影响（BF10=0.65）。在考虑到全局淀粉样蛋白 PET 信号后，我们发现 TDP-43 病理学对生前记忆表现有负效应，但这一效应只是偶然存在（BF10=1.6）。