Plasma N-terminal tau fragment levels predict future cognitive decline and neurodegeneration in healthy elderly individuals

Jasmeer P. Chhatwal, Aaron P. Schultz, Yifan Dang, Beth Ostaszewski, Lei Liu, Hyun-Sik Yang, Keith A. Johnson, Reisa A. Sperling () and Dennis J. Selkoe ()
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Jasmeer P. Chhatwal: Massachusetts General Hospital
Aaron P. Schultz: Massachusetts General Hospital
Yifan Dang: Brigham and Women’s Hospital
Beth Ostaszewski: Brigham and Women’s Hospital
Lei Liu: Brigham and Women’s Hospital
Hyun-Sik Yang: Massachusetts General Hospital
Keith A. Johnson: Massachusetts General Hospital
Reisa A. Sperling: Massachusetts General Hospital
Dennis J. Selkoe: Brigham and Women’s Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract The availability of blood-based assays detecting Alzheimer’s disease (AD) pathology should greatly accelerate AD therapeutic development and improve clinical care. This is especially true for markers that capture the risk of decline in pre-symptomatic stages of AD, as this would allow one to focus interventions on participants maximally at risk and at a stage prior to widespread synapse loss and neurodegeneration. Here we quantify plasma concentrations of an N-terminal fragment of tau (NT1) in a large, well-characterized cohort of clinically normal elderly who were followed longitudinally. Plasma NT1 levels at study entry (when all participants were unimpaired) were highly predictive of future cognitive decline, pathological tau accumulation, neurodegeneration, and transition to a diagnosis of MCI/AD. These predictive effects were particularly strong in participants with even modestly elevated brain β-amyloid burden at study entry, suggesting plasma NT1 levels capture very early cognitive, pathologic and neurodegenerative changes along the AD trajectory.

Date: 2020
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DOI: 10.1038/s41467-020-19543-w

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