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A new factor of genetic susceptibility to Alzheimer's disease
Date:11/19/2012

rformed in another independent series of 1994 cases and 4602 controls, which confirmed this strong association (OR=4.97 CI 95% [2.42-10.21], P<6.10-6).

These results are also confirmed in the same edition of The New England Journal of Medicine by an Icelandic team, which also shows that this gene is a risk factor for Alzheimer's disease in the Finnish population and other European populations.

A pathological analysis of six individuals presenting variants of the TREM2 gene has revealed evidence of Alzheimer's-type brain lesions. The study of TREM2 gene expression in normal human brains has shown high levels in the white matter and in the hippocampus and cortex.

In a transgenic mouse model of Alzheimer's disease, an increase in TREM2 expression was observed in microglial cells surrounding the amyloid plaques and the neurons compared with normal mice. The TREM2 gene encodes a protein that participates in the activation of immune responses in macrophages and dendritic cells.

This discovery has two main consequences. Firstly, this observation provides a better understanding of the immune system's involvement in Alzheimer's disease in which the gene of complement receptor 1 (CR1) had already been implicated, in previous work by Inserm-Lille2-IPL UMR744 . Furthermore, this approach of whole-exome sequencing has allowed the discovery of a gene for susceptibility to a rare disease that causes susceptibility to a common disease, evidence of the heterogeneous aetiology of Alzheimer's disease. It is the loss of function of this gene in its homozygous or heterozygous variants that determines the nature of the disorder.

These results, which demonstrate how much progress has been made in understanding Alzheimer's disease, involved teams from LabEx DISTALZ, and were able to be produced partly through the support of the French Foundation for Scientific Cooperation on Alzheimer's and similar diseases, launched in February 2008
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Contact: presse
presse@inserm.fr
INSERM (Institut national de la sant et de la recherche mdicale)
Source:Eurekalert

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