Prediction of amyloid and tau brain deposition and cognitive decline in people with Down syndrome using plasma biomarkers: a longitudinal cohort study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Plasma biomarkers associated with Alzheimer's disease could improve prognostic assessment for people with Down syndrome in both clinical practice and research settings. We aimed to identify the plasma biomarkers that most accurately predict longitudinal changes in Alzheimer's disease-related pathology and cognitive functioning in individuals with Down syndrome. Methods This longitudinal cohort study included data from 258 adults (aged ≥25 years) with Down syndrome who were followed up prospectively every 16 months as part of the longitudinal Alzheimer's Biomarker Consortium–Down Syndrome study (recruited from seven university sites in the USA and UK between July 13, 2016, and Jan 15, 2019). Participants had baseline and longitudinal assessments of plasma tau phosphorylated at threonine 217 (p-tau217), glial fibrillary acidic protein (GFAP), amyloid β (Aβ) 42/40 , neurofilament light (NfL), or total tau (t-tau). Associations of baseline plasma biomarkers and longitudinal changes in plasma biomarkers with changes in global cognitive functioning (Down Syndrome Mental Status Examination [DS-MSE] scores), Aβ-PET, and tau-PET were examined using linear regression models. Plasma biomarker-associated risk of progression to dementia was assessed using Cox regression analysis. Findings Baseline p-tau217, as well as GFAP, NfL, or t-tau, were individually associated with longitudinal changes in DS-MSE, Aβ-PET, and tau-PET, and with progression to dementia. However, in combined models, only baseline p-tau217 remained associated with changes in DS-MSE (β –0·30 [95% CI –0·45 to –0·15], p=0·0001, n=220), tau-PET (0·42 [0·14 to 0·70], p=0·0039, n=88), and progression to dementia (hazard ratio 3·51 [95% CI 1·76–7·00], p=0·0004, n=194), whereas baseline p-tau217 (0·29 [0·14–0·45], p=0·0003) and GFAP (0·37 [0·18–0·56], p=0·0003) were associated with changes in Aβ-PET (n=106 for both). Similar associations were shown between longitudinal p-tau217 or GFAP and changes in DS-MSE (p-tau217: β –0·33 [95% CI–0·52 to –0·13], p=0·0015, n=133), tau-PET (p-tau217: 0·61 [0·40 to 0·83], p<0·0001, n=87), and Aβ-PET (p-tau217: 0·35 [0·19 to 0·50], p<0·0001; GFAP: 0·49 [0·27 to 0·70], p<0·0001, n=88). Interpretation Baseline and longitudinal plasma p-tau217 were associated with subsequent decline in global cognition, progression to dementia, and increased tau burden, whereas baseline p-tau217 and GFAP were associated with Aβ accumulation. These findings suggest that plasma p-tau217 and GFAP might be valuable for prognostic assessment of Alzheimer's disease in people with Down syndrome in both clinical and research contexts. The results further support evaluation of these biomarkers for monitoring disease progression in clinical trials of Down syndrome-related Alzheimer's disease. Funding The European Research Council and National Institute on Aging (National Institute of Health).
Source: The Lancet Neurology
Authors: Shorena Janelidze, Lyduine E Collij, Niklas Mattsson-Carlgren, Alex Antill, Charles M Laymon, Ira Lott, H Diana Rosas, Davneet S Minhas, Weiquan Luo, Shahid Zaman, Mark Mapstone, Elizabeth Head, Florence Lai, Sigan L Hartley, Beau M Ances, Sharon J Krinsky-McHale, Joseph H Lee, Rik Ossenkoppele, Bradley T Christian, Benjamin L Handen, Oskar Hansson
Institutions: Lund University, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Skåne University Hospital, University of Pittsburgh, University of California, Irvine, Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, University of Cambridge, University of Wisconsin–Madison, Washington University in St. Louis, Columbia University Irving Medical Center, Columbia University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $7,280
Funders: Alzheimer's Association, Cure Alzheimer's Fund, GHR Foundation, Lunds Universitet, Hjärnfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Alzheimerfonden, Skånes universitetssjukhus, National Institutes of Health, Parkinsonfonden, European Research Council, National Institute on Aging, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, H2020 European Research Council
Awards: G1304444302, G1309605592, G1519619497, G1806104804, G1863874477, G3619923571, Novel biomarkers for improving diagnostics, prognostics, and treatments of Alzheimer’s disease, G4038479886, G4482953778, G5376167899, G6466923615, G6698537428, Prospective validation of high-performing blood biomarkers and digital cognitive tests in both specialist memory clinic and general primary care settings, G7153071485, G740574029, A precision medicine approach for the diagnosis and prognosis of preclinical Alzheimer´s disease with implications for clinical trials, G8919937767, G8946209249, Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS), National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W4411361815