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. 2024 Apr 14;16(2):e12582.
doi: 10.1002/dad2.12582. eCollection 2024 Apr-Jun.

Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome

Emily K Schworer  1 , Benjamin L Handen  2 , Melissa Petersen  3 , Sid O'Bryant  3 , Jamie C Peven  2 , Dana L Tudorascu  2 , Laisze Lee  2 , Sharon J Krinsky-McHale  4 , Christy L Hom  5 , Isabel C H Clare  6 , Bradley T Christian  1 , Nicole Schupf  7 , Joseph H Lee  7 , Elizabeth Head  8 , Mark Mapstone  9 , Ira Lott  9 , Beau M Ances  10 , Shahid Zaman  6 , Adam M Brickman  7 , Florence Lai  11 , H Diana Rosas  11   12 , Sigan L Hartley  1   13 ; Alzheimer Biomarker Consortium‐Down Syndrome
Affiliations

Cognitive and functional performance and plasma biomarkers of early Alzheimer's disease in Down syndrome

Emily K Schworer et al. Alzheimers Dement (Amst). .

Abstract

Introduction: People with Down syndrome (DS) have a 75% to 90% lifetime risk of Alzheimer's disease (AD). AD pathology begins a decade or more prior to onset of clinical AD dementia in people with DS. It is not clear if plasma biomarkers of AD pathology are correlated with early cognitive and functional impairments in DS, and if these biomarkers could be used to track the early stages of AD in DS or to inform inclusion criteria for clinical AD treatment trials.

Methods: This large cross-sectional cohort study investigated the associations between plasma biomarkers of amyloid beta (Aβ)42/40, total tau, and neurofilament light chain (NfL) and cognitive (episodic memory, visual-motor integration, and visuospatial abilities) and functional (adaptive behavior) impairments in 260 adults with DS without dementia (aged 25-81 years).

Results: In general linear models lower plasma Aβ42/40 was related to lower visuospatial ability, higher total tau was related to lower episodic memory, and higher NfL was related to lower visuospatial ability and lower episodic memory.

Discussion: Plasma biomarkers may have utility in tracking AD pathology associated with early stages of cognitive decline in adults with DS, although associations were modest.

Highlights: Plasma Alzheimer's disease (AD) biomarkers correlate with cognition prior to dementia in Down syndrome.Lower plasma amyloid beta 42/40 was related to lower visuospatial abilities.Higher plasma total tau and neurofilament light chain were associated with lower cognitive performance.Plasma biomarkers show potential for tracking early stages of AD symptomology.

Keywords: adaptive behavior; adults; cognitive performance; functional abilities; neurofilament light chain; plasma amyloid beta; plasma total tau; trisomy 21.

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Conflict of interest statement

No authors have conflicts of interest to disclose. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
A, Plasma Aβ42/40 and Block Design. B, Plasma total tau and mCRT. C, Plasma NfL and Block Design. D, Plasma NfL and mCRT. Aβ, amyloid beta; mCRT, modified Cued Recall Test; NfL, neurofilament light chain
See this image and copyright information in PMC

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