| Title: |
Comparison of tau spread in people with Down syndrome versus autosomal-dominant Alzheimer's disease: a cross-sectional study |
| Authors: |
Wisch, JK; McKay, NS; Boerwinkle, AH; Kennedy, J; Flores, S; Handen, BL; Christian, BT; Head, E; Mapstone, M; Rafii, MS; O'Bryant, SE; Price, JC; Laymon, CM; Krinsky-McHale, SJ; Lai, F; Rosas, HD; Hartley, SL; Zaman, S; Lott, IT; Tudorascu, D; Zammit, M; Brickman, AM; Lee, JH; Bird, TD; Cohen, A; Chrem, P; Daniels, A; Chhatwal, JP; Cruchaga, C; Ibanez, L; Jucker, M; Karch, CM; Day, GS; Levin, J; Llibre-Guerra, J; Li, Y; Lopera, F; Roh, JH; Ringman, JM; Supnet-Bell, C; van Dyck, CH; Xiong, C; Wang, G; Morris, JC; McDade, E; Bateman, RJ; Benzinger, TLS; Gordon, BA; Aizenstein, HJ; Andrews, HF; Ances, BM; Birn, RM; Bulova, P; Cheema, A; Chen, K; Clare, I; Clark, L; Cohen, AD; Constantino, JN; Doran, EW; Feingold, E; Foroud, TM; Hom, C; Honig, L; Ikonomovic, MD; Johnson, SC; Jordan, C; Kamboh, MI; Keator, D; Klunk, WE; Kofler, JK; Kreisl, WC; Lao, P; Lupson, V; Mathis, CA; Minhas, DS; Nadkarni, N; Pang, D; Petersen, M; Pulsifer, M; Reiman, E; Rizvi, B; Sabbagh, MN; Schupf, N; Tumuluru, R; Tycko, B; Varadarajan, B; White, DA; Yassa, MA; Zhang, F; Bateman, R; Daniels, AJ; Courtney, L |
| Source: |
The Lancet Neurology , 23 (5) pp. 500-510. (2024) |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Description: |
BACKGROUND: In people with genetic forms of Alzheimer's disease, such as in Down syndrome and autosomal-dominant Alzheimer's disease, pathological changes specific to Alzheimer's disease (ie, accumulation of amyloid and tau) occur in the brain at a young age, when comorbidities related to ageing are not present. Studies including these cohorts could, therefore, improve our understanding of the early pathogenesis of Alzheimer's disease and be useful when designing preventive interventions targeted at disease pathology or when planning clinical trials. We compared the magnitude, spatial extent, and temporal ordering of tau spread in people with Down syndrome and autosomal-dominant Alzheimer's disease. METHODS: In this cross-sectional observational study, we included participants (aged ≥25 years) from two cohort studies. First, we collected data from the Dominantly Inherited Alzheimer's Network studies (DIAN-OBS and DIAN-TU), which include carriers of autosomal-dominant Alzheimer's disease genetic mutations and non-carrier familial controls recruited in Australia, Europe, and the USA between 2008 and 2022. Second, we collected data from the Alzheimer Biomarkers Consortium–Down Syndrome study, which includes people with Down syndrome and sibling controls recruited from the UK and USA between 2015 and 2021. Controls from the two studies were combined into a single group of familial controls. All participants had completed structural MRI and tau PET (18F-flortaucipir) imaging. We applied Gaussian mixture modelling to identify regions of high tau PET burden and regions with the earliest changes in tau binding for each cohort separately. We estimated regional tau PET burden as a function of cortical amyloid burden for both cohorts. Finally, we compared the temporal pattern of tau PET burden relative to that of amyloid. FINDINGS: We included 137 people with Down syndrome (mean age 38·5 years [SD 8·2], 74 [54%] male, and 63 [46%] female), 49 individuals with autosomal-dominant Alzheimer's disease (mean age 43·9 years ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10208569/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10208569/2/Cash_Comparison%20of%20tau%20spread%20in%20people%20with%20Down%20syndrome%20versus%20autosomal-dominant%20Alzheimer%27s%20disease_AAM.pdf; https://discovery.ucl.ac.uk/id/eprint/10208569/ |
| Rights: |
open |
| Accession Number: |
edsbas.FFECE386 |
| Database: |
BASE |