학술논문
Comparison of amyloid burden in individuals with Down syndrome versus autosomal dominant Alzheimer's disease: a cross-sectional study
Document Type
article
Author
Boerwinkle, Anna H; Gordon, Brian A; Wisch, Julie; Flores, Shaney; Henson, Rachel L; Butt, Omar H; McKay, Nicole; Chen, Charles D; Benzinger, Tammie LS; Fagan, Anne M; Handen, Benjamin L; Christian, Bradley T; Head, Elizabeth; Mapstone, Mark; Rafii, Michael S; O'Bryant, Sid; Lai, Florence; Rosas, H Diana; Lee, Joseph H; Silverman, Wayne; Brickman, Adam M; Chhatwal, Jasmeer P; Cruchaga, Carlos; Perrin, Richard J; Xiong, Chengjie; Hassenstab, Jason; McDade, Eric; Bateman, Randall J; Ances, Beau M; Syndrome, Alzheimer's Biomarker Consortium-Down; Aizenstein, Howard J; Andrews, Howard F; Bell, Karen; Birn, Rasmus M; Bulova, Peter; Cheema, Amrita; Chen, Kewei; Clare, Isabel; Clark, Lorraine; Cohen, Ann D; Constantino, John N; Doran, Eric W; Feingold, Eleanor; Foroud, Tatiana M; Hartley, Sigan L; Hom, Christy; Honig, Lawrence; Ikonomovic, Milos D; Johnson, Sterling C; Jordan, Courtney; Kamboh, M Ilyas; Keator, David; Klunk, William E; Kofler, Julia K; Kreisl, William C; McHale, Sharon J Krinsky-; Lao, Patrick; Laymon, Charles; Lott, Ira T; Lupson, Victoria; Mathis, Chester A; Minhas, Davneet S; Nadkarni, Neelesh; Pang, Deborah; Petersen, Melissa; Price, Julie C; Pulsifer, Margaret; Reiman, Eric; Rizvi, Batool; Sabbagh, Marwan N; Schupf, Nicole; Tudorascu, Dana L; Tumuluru, Rameshwari; Tycko, Benjamin; Varadarajan, Badri; White, Desiree A; Yassa, Michael A; Zaman, Shahid; Zhang, Fan; Network, Dominantly Inherited Alzheimer; Adams, Sarah; Allegri, Ricardo; Araki, Aki; Barthelemy, Nicolas; Bechara, Jacob; Berman, Sarah; Bodge, Courtney; Brandon, Susan; Brooks, William; Brosch, Jared; Buck, Jill; Buckles, Virginia; Carter, Kathleen; Cash, Lisa; Mendez, Patricio C; Chua, Jasmin; Chui, Helena; Courtney, Laura; Day, Gregory; DeLaCruz, Chrismary
Source
The Lancet Neurology. 22(1)
Subject
Language
Abstract
BackgroundImportant insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.MethodsIn this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.Findings192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p