Plasma NT1-tau and Aβ42 correlate with age and cognitive function in two large Down syndrome cohorts

Andrew M. Stern; Kathryn L. Van Pelt; Lei Liu; Amirah K. Anderson; Beth Ostaszewski; Mark Mapstone; Sid O'Bryant; Melissa E. Petersen; Bradley T. Christian; Benjamin L. Handen; Dennis J. Selkoe; Frederick Schmitt; Elizabeth Head

doi:10.1002/alz.13382

Plasma NT1-tau and Aβ₄₂ correlate with age and cognitive function in two large Down syndrome cohorts

Andrew M. Stern, Kathryn L. Van Pelt, Lei Liu, Amirah K. Anderson, Beth Ostaszewski, Mark Mapstone, Sid O'Bryant, Melissa E. Petersen, Bradley T. Christian, Benjamin L. Handen, Dennis J. Selkoe, Frederick Schmitt, Elizabeth Head

Research output: Contribution to journal › Article › peer-review

Abstract

INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, Aβ₃₇, Aβ₄₀, and Aβ₄₂ levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, Aβ₄₂, and Aβ_37:42 were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and Aβ₄₂ decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.

Original language	English
Pages (from-to)	5755-5764
Number of pages	10
Journal	Alzheimer's and Dementia
Volume	19
Issue number	12
DOIs	https://doi.org/10.1002/alz.13382
State	Published - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Keywords

Alzheimer disease
Aβ
Down syndrome
biomarker
plasma
tau

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/alz.13382

Cite this

Stern, A. M., Van Pelt, K. L., Liu, L., Anderson, A. K., Ostaszewski, B., Mapstone, M., O'Bryant, S., Petersen, M. E., Christian, B. T., Handen, B. L., Selkoe, D. J., Schmitt, F., & Head, E. (2023). Plasma NT1-tau and Aβ₄₂ correlate with age and cognitive function in two large Down syndrome cohorts. Alzheimer's and Dementia, 19(12), 5755-5764. https://doi.org/10.1002/alz.13382

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abstract = "INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and Aβ42 decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.",

keywords = "Alzheimer disease, Aβ, Down syndrome, biomarker, plasma, tau",

author = "Stern, {Andrew M.} and {Van Pelt}, {Kathryn L.} and Lei Liu and Anderson, {Amirah K.} and Beth Ostaszewski and Mark Mapstone and Sid O'Bryant and Petersen, {Melissa E.} and Christian, {Bradley T.} and Handen, {Benjamin L.} and Selkoe, {Dennis J.} and Frederick Schmitt and Elizabeth Head",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

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doi = "10.1002/alz.13382",

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AU - Ostaszewski, Beth

AU - Mapstone, Mark

AU - O'Bryant, Sid

AU - Petersen, Melissa E.

AU - Christian, Bradley T.

AU - Handen, Benjamin L.

AU - Selkoe, Dennis J.

AU - Schmitt, Frederick

AU - Head, Elizabeth

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N2 - INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and Aβ42 decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.

AB - INTRODUCTION: People with Down syndrome (DS) often develop Alzheimer's disease (AD). Here, we asked whether ultrasensitive plasma immunoassays for a tau N-terminal fragment (NT1-tau) and Aβ isoforms predict cognitive impairment. METHODS: Plasma NT1-tau, Aβ37, Aβ40, and Aβ42 levels were measured in a longitudinal discovery cohort (N = 85 participants, 220 samples) and a cross-sectional validation cohort (N = 239). We developed linear models and predicted values in the validation cohort. RESULTS: Discovery cohort linear mixed models for NT1-tau, Aβ42, and Aβ37:42 were significant for age; there was no main effect of time. In cross-sectional models, NT1-tau increased and Aβ42 decreased with age. NT1-tau predicted cognitive and functional scores. The discovery cohort linear model for NT1-tau predicted levels in the validation cohort. DISCUSSION: NT1-tau correlates with age and worse cognition in DS. Further validation of NT1-tau and other plasma biomarkers of AD neuropathology in DS cohorts is important for clinical utility.

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