Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Plasma levels of an N-terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Schultz Stephanie A, Rao Yiwen, Liu Lei, Ostaszewski Beth, Anderson Amirah K, Yau Wai-Ying Wendy, Shirzadi Zahra, Gordon Brian A, Hassenstab Jason, Morris John C, Perrin Richard J, Allegri Ricardo F, Barthélemy Nicolas R, Fox Nick, Day Gregory S, Jucker Mathias, Levey Allan I, Levin Johannes, Mori Hiroshi, Salloway Stephen, Schofield Peter, McDade Eric, Sperling Reisa A, Bateman Randall J, Selkoe Dennis J, Chhatwal Jasmeer P, and the Dominantly Inherited Alzheimer's Network
Аннотация
INTRODUCTION: 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).
METHODS: 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).
RESULTS: 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.
DISCUSSION: 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.
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.
METHODS: 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).
RESULTS: 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.
DISCUSSION: 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.
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.