Dissociable influences of APOE ε4 and polygenic risk of AD dementia on amyloid and cognition
作者： Tian Ge , Mert R Sabuncu , Jordan W Smoller , Reisa A Sperling , Elizabeth C Mormino
DOI: 10.1212/WNL.0000000000005415
关键词:
摘要: Objective To investigate the effects of genetic risk Alzheimer disease (AD) dementia in context β-amyloid (Aβ) accumulation. Methods We analyzed data from 702 participants (221 clinically normal, 367 with mild cognitive impairment, and 114 AD dementia) florbetapir PET available. A subset 669 additionally had longitudinal MRI scans to assess hippocampal volume. Polygenic scores (PRSs) were estimated summary statistics previous large-scale genome-wide association studies dementia. examined relationships between APOE e4 status PRS Aβ volume measurements. Results was strongly related baseline Aβ, whereas only weak associations present. greater memory decline atrophy Aβ+ participants. When controlled for, Finally, PRSs associated Aβ− weakly Conclusions Genetic factors demonstrate as well synergistic interactions Aβ. The specific effect faster individuals higher may explain large degree heterogeneity trajectories among individuals. Consideration variants conjunction improve enrichment strategies for clinical trials targeting most at imminent decline.
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