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@ARTICLE{Schultz:283157,
author = {Schultz, Stephanie A and Rao, Yiwen and Liu, Lei and
Ostaszewski, Beth and Anderson, Amirah K and Yau, Wai-Ying
Wendy and Shirzadi, Zahra and Gordon, Brian A and
Hassenstab, Jason and Morris, John C and Perrin, Richard J
and Allegri, Ricardo F and Barthélemy, Nicolas R and Fox,
Nick and Day, Gregory S and Jucker, Mathias and Levey, Allan
I and Levin, Johannes and Mori, Hiroshi and Salloway,
Stephen and Schofield, Peter and McDade, Eric and Sperling,
Reisa A and Bateman, Randall J and Selkoe, Dennis J and
Chhatwal, Jasmeer P},
collaboration = {Network, and the Dominantly Inherited Alzheimer's},
title = {{P}lasma levels of an {N}-terminal tau fragment predict
{A}lzheimer's and neurodegenerative disease biomarkers in
autosomal dominant {A}lzheimer's disease.},
journal = {Alzheimer's and dementia},
volume = {22},
number = {1},
issn = {1552-5260},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DZNE-2026-00053},
pages = {e71049},
year = {2026},
abstract = {Tau 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).Here, 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).NT1 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.Together, 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.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.},
keywords = {Humans / tau Proteins: blood / Alzheimer Disease: blood /
Alzheimer Disease: genetics / Alzheimer Disease: diagnosis /
Biomarkers: blood / Male / Female / Cross-Sectional Studies
/ Middle Aged / Longitudinal Studies / Peptide Fragments:
blood / Aged / Neurodegenerative Diseases: blood / ADAD
(Other) / biomarker (Other) / neurodegeneration (Other) /
tauopathy (Other) / tau Proteins (NLM Chemicals) /
Biomarkers (NLM Chemicals) / Peptide Fragments (NLM
Chemicals) / MAPT protein, human (NLM Chemicals)},
cin = {AG Jucker / Clinical Research (Munich) / AG Levin},
ddc = {610},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1111015 /
I:(DE-2719)1111016},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)DIAN-20090101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41505233},
doi = {10.1002/alz.71049},
url = {https://pub.dzne.de/record/283157},
}