Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.
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ABSTRACT: Introduction
The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and 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 = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau.Results
No clear evidence that Aβ40 or Aβ42 directly causes changes in t-Tau was observed; the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL.Discussion
Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau. In contrast, Aβ aggregation may causally impact NFL in cognitively unimpaired men in their late 60s.
SUBMITTER: Gillespie NA
PROVIDER: S-EPMC11291022 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
Publications
Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.
Gillespie Nathan A NA Neale Michael C MC Panizzon Matthew S MS McKenzie Ruth E RE Tu Xin M XM Xian Hong H Reynolds Chandra A CA Lyons Michael J MJ Rissman Robert A RA Elman Jeremy A JA Franz Carol C Kremen William S WS
bioRxiv : the preprint server for biology 20240726
<h4>Introduction</h4>The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.<h4>Methods</h4>Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causati ...[more]
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