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

Author:

Schworer Emily K.1ORCID,Handen Benjamin L.2,Petersen Melissa3,O'Bryant Sid3,Peven Jamie C.2,Tudorascu Dana L.2,Lee Laisze2,Krinsky‐McHale Sharon J.4,Hom Christy L.5,Clare Isabel C. H.6,Christian Bradley T.1,Schupf Nicole7,Lee Joseph H.7,Head Elizabeth8,Mapstone Mark9,Lott Ira9,Ances Beau M.10,Zaman Shahid6,Brickman Adam M.7,Lai Florence11,Rosas H. Diana1112,Hartley Sigan L.113,

Affiliation:

1. Waisman Center University of Wisconsin‐Madison Madison Wisconsin USA

2. Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA

3. Department of Family Medicine and Institute for Translational Research University of North Texas Health Science Center Fort Worth Texas USA

4. New York State Institute for Basic Research in Developmental Disabilities Staten Island New York USA

5. Department of Psychiatry and Human Behavior University of California Irvine California USA

6. Department of Psychiatry University of Cambridge Cambridge UK

7. Taub Institute for Research on Alzheimer's Disease and the Aging Brain Sergievsky Center and Department of Neurology Vagelos College of Physicians and Surgeons Columbia University New York New York USA

8. Department of Pathology & Laboratory Medicine University of California Irvine School of Medicine Irvine California USA

9. Department of Neurology University of California Irvine School of Medicine Irvine California USA

10. Department of Neurology Washington University at St. Louis St. Louis Missouri USA

11. Department of Neurology Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA

12. Center for Neuro‐imaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA

13. School of Human Ecology University of Wisconsin‐Madison Madison Wisconsin USA

Abstract

AbstractINTRODUCTIONPeople 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.METHODSThis 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).RESULTSIn 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.DISCUSSIONPlasma 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.

Funder

National Institute on Aging

NIHR Cambridge Biomedical Research Centre

Publisher

Wiley

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