Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.

bioRxiv - Pathology Pub Date : 2024-07-26 DOI:10.1101/2024.07.23.602498

Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen

引用次数: 0

Abstract

INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.

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利用具有遗传信息的成年男性双胞胎样本，测试淀粉样变性对总 Tau 的因果影响。

简介：淀粉样蛋白级联假说预测淀粉样蛋白-β（Aβ）的聚集会推动tau纠结的积累。我们就 Aβ40 和 Aβ42 与总 Tau（t-Tau）血浆生物标志物之间的因果关系方向测试了相互竞争的非因果假说。方法：使用 Simoa 人类神经学 3-plex A 免疫测定法测定了 1,035 名男性（平均年龄 67.0 岁，范围 60-73）的血浆 Aβ40、Aβ42、t-Tau 和神经丝轻链 (NFL)。遗传信息双胞胎模型检验了 Aβ 和 t-Tau 之间的因果关系。结果：没有确凿证据证明 Aβ40 或 Aβ42 对 t-Tau 有因果影响。探索性分析表明 Aβ 生物标志物对 NFL 有因果影响，t-Tau 和 NFL 之间存在互为因果关系。讨论：血浆 Aβ40 和 Aβ42 水平似乎不会对 t-Tau 产生因果影响。然而，对于 67 岁左右认知能力未受损、居住在社区的男性来说，Aβ聚集可能会对 NFL 产生因果影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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bioRxiv - Pathology

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