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

Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology. In our functional dissection of the CD33 Alzhei...

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Published in	Nature neuroscience Vol. 16; no. 7; pp. 848 - 850
Main Authors	Bradshaw, Elizabeth M, Chibnik, Lori B, Keenan, Brendan T, Ottoboni, Linda, Raj, Towfique, Tang, Anna, Rosenkrantz, Laura L, Imboywa, Selina, Lee, Michelle, Von Korff, Alina, Morris, Martha C, Evans, Denis A, Johnson, Keith, Sperling, Reisa A, Schneider, Julie A, Bennett, David A, De Jager, Philip L
Format	Journal Article
Language	English
Published	New York Nature Publishing Group US 01.07.2013 Nature Publishing Group
Subjects	631/378/1689/1283 631/378/2596/1953 631/378/340 692/420/2489/144 Adult Age Factors Aged Aged, 80 and over Aging Alzheimer Disease - diagnostic imaging Alzheimer Disease - genetics Alzheimer Disease - pathology Alzheimer's disease Amyloid beta-Peptides - metabolism Amyloid beta-protein Aniline Compounds Animal Genetics and Genomics Behavioral Sciences Biological Techniques Biomedicine Brain - diagnostic imaging Brain - pathology brief-communication Cell receptors Cognitive Dysfunction - metabolism Cognitive Dysfunction - pathology Cohort Studies Dextrans - metabolism Disease Female Genetic aspects Genetic Association Studies Genotype Genotype & phenotype HLA-D Antigens - metabolism Hospitals Humans Immune system Male Microglia - pathology Middle Aged Monocytes Monocytes - metabolism Neurobiology Neurology Neurosciences Peptide Fragments - metabolism Physiological aspects Plaque, Amyloid - pathology Polymorphism, Genetic - genetics Radionuclide Imaging Sialic Acid Binding Ig-like Lectin 3 - genetics Sialic Acid Binding Ig-like Lectin 3 - metabolism Thiazoles Young Adult Chicago Illinois United States > US Massachusetts Illinois
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ISSN	1097-6256 1546-1726 1546-1726
DOI	10.1038/nn.3435

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Summary:	Genome-wide association studies have identified CD33 as an Alzheimer's disease susceptibility locus. Here, the authors show that the CD33 risk allele is associated with altered myeloid function, microglial activation and in vivo amyloid pathology. 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 × 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
ISSN:	1097-6256 1546-1726 1546-1726
DOI:	10.1038/nn.3435