Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Joseph-Mathurin Nelly, Feldman Rebecca L, Lu Ruijin, Shirzadi Zahra, Toomer Carmen, Saint Clair Junie R, Ma Yinjiao, McKay Nicole S, Strain Jeremy F, Kilgore Collin, Friedrichsen Karl A, Chen Charles D, Gordon Brian A, Chen Gengsheng, Hornbeck Russ C, Massoumzadeh Parinaz, McCullough Austin A, Wang Qing, Li Yan, Wang Guoqiao, Keefe Sarah J, Schultz Stephanie A, Cruchaga Carlos, Preboske Gregory M, Jack Clifford R, Llibre-Guerra Jorge J, Allegri Ricardo F, Ances Beau M, Berman Sarah B, Brooks William S, Cash David M, Day Gregory S, Fox Nick C, Fulham Michael, Ghetti Bernardino, Johnson Keith A, Jucker Mathias, Klunk William E, la Fougère Christian, Levin Johannes, Niimi Yoshiki, Oh Hwamee, Perrin Richard J, Reischl Gerald, Ringman John M, Saykin Andrew J, Schofield Peter R, Su Yi, Supnet-Bell Charlene, Vöglein Jonathan, Yakushev Igor, Brickman Adam M, Morris John C, McDade Eric, Xiong Chengjie, Bateman Randall J, Chhatwal Jasmeer P, Benzinger Tammie L S, Dominantly Inherited Alzheimer Network
Аннотация
METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition.
RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures.
DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials.
HIGHLIGHTS: Mutation position influences Aβ burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aβ burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.