Journal Article

DZNE-2026-00581

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Plasma levels of an N‐terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease

Schultz, S. A. ; Rao, Y. ; Liu, L. ; Ostaszewski, B. ; Anderson, A. K. ; Yau, W. W. ; Shirzadi, Z. ; Gordon, B. A. ; Hassenstab, J. ; Morris, J. C. ; Perrin, R. J. ; Allegri, R. F. ; Barthélemy, N. R. ; Fox, N. ; Day, G. S. ; Jucker, M.DZNE* ; Levey, A. I. ; Levin, J.DZNE* ; Mori, H. ; Salloway, S. ; Schofield, P. ; McDade, E. ; Sperling, R. A. ; Bateman, R. J. ; Selkoe, D. J. ; Chhatwal, J. P.

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71049

Abstract: INTRODUCTIONTau species lacking truncation of the N-terminal region, including plasma N-terminal tau fragment 1 (NT1), have been previously associated with cognitive decline, neurodegeneration, and tau pathology in late-onset sporadic Alzheimer's disease (AD).METHODSHere, we examined cross-sectional and longitudinal plasma NT1 as a possible predictor of cognitive, clinical, and core AD biomarker trajectories in autosomal dominant AD (ADAD).RESULTSNT1 levels in ADAD mutation carriers (MC; n = 132) increased across the disease continuum, compared to non-carriers (NC; n = 75), becoming elevated about a decade prior to estimated symptom onset. Cross-sectional and longitudinal NT1 levels in MC were associated with clinical, cognitive, and biomarker changes. NT1 increases continued in symptomatic phases of disease, a distinct trajectory from that seen with CSF p-tau217 and other phospho-tau species.DISCUSSIONTogether, our results suggest that plasma NT1—alone or combined with other tau measures—may be useful in studying AD-related clinical, cognitive, and biomarker outcomes.Highlights Leveraging a deeply phenotyped cohort of individuals carrying a pathogenic variant for autosomal dominant Alzheimer's disease (ADAD) and their non-carrier family members, our results suggest that plasma N-terminal tau fragment 1 (NT1) levels mirrored changes in clinical, cognitive, and neurodegenerative measures in ADAD, particularly in late asymptomatic and early symptomatic phases of disease. NT1 levels correlated with cerebrospinal fluid (CSF) measures of tau pathology but less so with CSF or imaging measures of β-amyloid pathology. Together with previous supportive findings in preclinical and symptomatic sporadic AD, these results suggest that plasma NT1—alone or combined with other tau measures—may be useful in studying AD-related tau pathology and neurodegeneration across a wide spectrum of disease.

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Contributing Institute(s):

1. Clinical Neurodegeneration (AG Levin)
2. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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