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CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. 2013
Elizabeth M Bradshaw, and
Lori B Chibnik, and
Brendan T Keenan, and
Linda Ottoboni, and
Towfique Raj, and
Anna Tang, and
Laura L Rosenkrantz, and
Selina Imboywa, and
Michelle Lee, and
Alina Von Korff, and
, and
Martha C Morris, and
Denis A Evans, and
Keith Johnson, and
Reisa A Sperling, and
Julie A Schneider, and
David A Bennett, and
Philip L De Jager
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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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