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Nat Neurosci. 2015 Nov;18(11):1556-8. doi: 10.1038/nn.4126. Epub 2015 Sep 28.

CD33 modulates TREM2: convergence of Alzheimer loci.

Chan G1,2,3,4,5, White CC1,2,3,4, Winn PA1,2,3,4, Cimpean M1,2,3,4, Replogle JM1,2,3,4,5, Glick LR1,2,3,4, Cuerdon NE1,2,3,4, Ryan KJ1,2,3,4,5, Johnson KA5,6,7, Schneider JA8, Bennett DA8, Chibnik LB1,2,3,4,5, Sperling RA5,6,7, Bradshaw EM1,2,3,4,5, De Jager PL1,2,3,4,5.

Author information

1
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
2
Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
3
Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
4
Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
5
Harvard Medical School, Boston, Massachusetts, USA.
6
Center for Alzheimer's Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
7
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
8
Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

Abstract

We used a protein quantitative trait analysis in monocytes from 226 individuals to evaluate cross-talk between Alzheimer loci. The NME8 locus influenced PTK2B and the CD33 risk allele led to greater TREM2 expression. There was also a decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid pathology.

PMID:
26414614
PMCID:
PMC4682915
DOI:
10.1038/nn.4126
[Indexed for MEDLINE]
Free PMC Article

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