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Marjorie Bekaert Thomas
Advances in health and medicine.
Neurological Disorders Channel
Reported January 11, 2013

New Variants in Alzheimer’s Disease


(Ivanhoe Newswire) – Alzheimer’s disease is the most common cause of dementia.  It is a complex disorder with a strong genetic component.  Researchers have announced that homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early onset dementia.
The study examined 1,092 patients with Alzheimer’s and used 1,107 patients as the control.  Scientists used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in the 1, 092 patients.  They then performed a meta-analysis on data for the TREM2 variant (predicted to cause a R47H substitution) from 3 genome studies of Alzheimer’s disease and tested for the association of the variant with the disease. 
Researchers genotyped the R47H variant in additional cases in 1,887 patients with Alzheimer’s and 4,061 as the controls.  They cross referenced the expression of TREM2 across different regions of the human brain and identified genes that are differently expressed in mice with Alzheimer’s and in control mice.
Researchers found more variants in exon 2 of TREM2 in patients with Alzheimer’s than in the control.  Out of the 1,092 participants with the disease, 22 variants were found.  Five variants were found in the 1,107 control participants.  The R47H showed significantly higher associations with Alzheimer’s.  The meta-analysis of the R47H and the additional series of 1,887 patients with the disease and 4,061 patients as the control confirmed this association.  
In conclusion, the rare variants in TREM2 are associated with an increase in the risk of Alzheimer’s disease.  
SOURCE:  New England Journal of Medicine, January 2013


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