AD: Large international collaboration allows identification of a new gene associated with Alzheimer’s disease

ARUKImage supplied by Alzheimer’s Research UK  in the article “Global research team discovers new Alzheimer’s risk gene”

TREM2  Variants in Alzheimer’s Disease

Rita Guerreiro, Ph.D., Aleksandra Wojtas, M.S., Jose Bras, Ph.D., Minerva Carrasquillo, Ph.D., Ekaterina Rogaeva, Ph.D., Elisa Majounie, Ph.D., Carlos Cruchaga, Ph.D., Celeste Sassi, M.D., John S.K. Kauwe, Ph.D., Steven Younkin, M.D., Ph.D., Lilinaz Hazrati, M.D., Ph.D., John Collinge, M.D., Jennifer Pocock, Ph.D., Tammaryn Lashley, Ph.D., Julie Williams, Ph.D., Jean-Charles Lambert, Ph.D., Philippe Amouyel, M.D., Ph.D., Alison Goate, Ph.D., Rosa Rademakers, Ph.D., Kevin Morgan, Ph.D., John Powell, Ph.D., Peter St. George-Hyslop, M.D., Andrew Singleton, Ph.D., and John Hardy, Ph.D.

New England Journal of Medicine, 14 Nov 2012

As part of a large collaboration between different groups across the globe, we at the UCL’s Institute of Neurology were able to associate a rare variant in the gene TREM2 with an increased risk of developing Alzheimer’s disease.

By applying new technologies, we studied data from more than 25,000 people: we started by sequencing the genes of 1,092 people with Alzheimer’s and a control group of 1,107 healthy people. The results showed that several mutations in the TREM2 gene occurred more frequently in people who had the disease than in those without the disease. One specific mutation, known as R47H, had a particularly strong association with the disease – appearing in 2% of people with Alzheimer’s compared to 0.5% of people without the disease. We then confirmed these findings in two larger independent groups, analyzing data from other 6,675 people with Alzheimer’s and 16,242 people without the disease. Again, the R47H variant was more likely to appear in people affected by Alzheimer’s than in people without the disease.

The mutation now identified is very rare (occurs in only 0.3-0.5% of the population) but it increases the likelihood of developing Alzheimer’s disease by three fold – more than any of the genes that have been linked to Alzheimer’s in the last 20 years.

These findings are particularly interesting because they clearly point towards previously unrecognized players and pathways underlying Alzheimer’s disease. This will help us to understand of what goes wrong in Alzheimer’s disease and to find ways to prevent or treat the disease.

Summary contributed by the first author of the paper, Rita Guerreiro.


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