CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

CD33 阿尔茨海默病基因座:单核细胞功能和淀粉样蛋白生物学改变

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作者:Elizabeth M Bradshaw, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa, Michelle Lee, Alina Von Korff; Alzheimer Disease Neuroimaging Initiative; Martha C Morris, Denis A Evans, Keith Johnson, Reisa A Sperling, Julie A Schneider, David A

Abstract

In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

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