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

Author:

Chhatwal Jasmeer P.ORCID,Schultz Aaron P.,Dang Yifan,Ostaszewski Beth,Liu LeiORCID,Yang Hyun-SikORCID,Johnson Keith A.,Sperling Reisa A.,Selkoe Dennis J.

Abstract

AbstractThe 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute on Aging

Doris Duke Charitable Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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