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

被引：451

作者：

Bradshaw, Elizabeth M. ^{[1
,2
,3
,4
]}

Chibnik, Lori B. ^{[1
,2
,3
,4
]}

Keenan, Brendan T. ^{[1
,2
,4
]}

Ottoboni, Linda ^{[1
,2
,3
,4
]}

Raj, Towfique ^{[1
,2
,3
,4
]}

Tang, Anna ^{[1
,2
,4
]}

Rosenkrantz, Laura L. ^{[1
,2
,4
]}

Imboywa, Selina ^{[1
,2
,4
]}

Lee, Michelle ^{[1
,2
]}

Von Korff, Alina ^{[1
,2
]}

Morris, Martha C. ^{[5
]}

Evans, Denis A. ^{[6
]}

Johnson, Keith ^{[3
,7
,9
]}

Sperling, Reisa A. ^{[3
,7
,8
,9
]}

Schneider, Julie A. ^{[5
]}

Bennett, David A. ^{[5
]}

De Jager, Philip L. ^{[1
,2
,3
,4
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Neurol, Inst Neurosci, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[5] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[6] Rush Univ, Med Ctr, Rush Inst Hlth Aging, Chicago, IL 60612 USA

[7] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[8] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimers Res & Treatment, Boston, MA 02115 USA

[9] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA

来源：

NATURE NEUROSCIENCE | 2013年 / 16卷 / 07期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; COGNITIVE IMPAIRMENT; IDENTIFIES VARIANTS; COMMON VARIANTS; EPHA1; PET; DEMENTIA; BINDING; CD2AP; BETA;

D O I：

10.1038/nn.3435

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 ( t(50) = 10.06, P-joint = 1.3 x 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-beta 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

引用

页码：848 / U92

页数：5

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