TY  - JOUR
AU  - Schultz, Stephanie A
AU  - Rao, Yiwen
AU  - Liu, Lei
AU  - Ostaszewski, Beth
AU  - Anderson, Amirah K
AU  - Yau, Wai-Ying Wendy
AU  - Shirzadi, Zahra
AU  - Gordon, Brian A
AU  - Hassenstab, Jason
AU  - Morris, John C
AU  - Perrin, Richard J
AU  - Allegri, Ricardo F
AU  - Barthélemy, Nicolas R
AU  - Fox, Nick
AU  - Day, Gregory S
AU  - Jucker, Mathias
AU  - Levey, Allan I
AU  - Levin, Johannes
AU  - Mori, Hiroshi
AU  - Salloway, Stephen
AU  - Schofield, Peter
AU  - McDade, Eric
AU  - Sperling, Reisa A
AU  - Bateman, Randall J
AU  - Selkoe, Dennis J
AU  - Chhatwal, Jasmeer P
TI  - Plasma levels of an N-terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease.
JO  - Alzheimer's and dementia
VL  - 22
IS  - 1
SN  - 1552-5260
CY  - Hoboken, NJ
PB  - Wiley
M1  - DZNE-2026-00053
SP  - e71049
PY  - 2026
AB  - 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.
KW  - Humans
KW  - tau Proteins: blood
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: diagnosis
KW  - Biomarkers: blood
KW  - Male
KW  - Female
KW  - Cross-Sectional Studies
KW  - Middle Aged
KW  - Longitudinal Studies
KW  - Peptide Fragments: blood
KW  - Aged
KW  - Neurodegenerative Diseases: blood
KW  - ADAD (Other)
KW  - biomarker (Other)
KW  - neurodegeneration (Other)
KW  - tauopathy (Other)
KW  - tau Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41505233
DO  - DOI:10.1002/alz.71049
UR  - https://pub.dzne.de/record/283157
ER  -