Gene that increases Alzheimer’s risk in women identified

By Mark Waghorn via SWNS

A gene that increases the risk of Alzheimer's in women has been identified by scientists.

The discovery opens the door to a screening program - and it could also hold the key to why females are disproportionately affected.

Nearly two-thirds of patients living with dementia are women - a phenomenon that has baffled scientists for decades.

The gene, named MGMT, is involved in repairing damage to DNA damage. It also fuels amyloid beta and tau - rogue proteins linked to Alzheimer's.

The phenomenon happens in women - rather than men. Over-production leads to aggregations of clumps and tangles, respectively - killing neurons.

Senior author Dr. Lindsay Farrer, of the University of Boston, said: "This is one of a few and perhaps the strongest associations of a genetic risk factor for Alzheimer's that is specific to women.

"This finding is particularly robust because it was discovered independently in two distinct populations using different approaches."

It was based on a genome-wide association study (GWAS) that looked for variations in DNA.

The US team looked at a large extended family of Hutterites - a founder population of central European ancestry who settled in the mid-west 150 years ago.

They are often analyzed for genetic determinants of disease because they have a relatively small gene pool due to their isolated, insular culture. For the purpose of the study, all individuals with Alzheimer's were women.

Dr. Farrer and colleagues also looked at another set of genetic data on 10,340 women across the country who lacked the APOE ε4 mutation linked to Alzheimer's.

In both groups, a gene known as MGMT was significantly associated with developing Alzheimer's.

Dr. Farrer said: "While the finding in the large dataset was most pronounced in women who don’t have APOE ε4, the Hutterite sample was too small to evaluate this pattern with any certainty."

The number of dementia cases worldwide will triple to more than 150 million by 2050. There is no cure.

There are currently over 5.8 million sufferers in the US.

Identifying those most at risk could lead to new therapies. Drugs trials have failed to date because they are prescribed too late - once the disease has taken hold.

Scientists have discovered other genes that increase the risk - the most well-known of which is APOE ε4.

Around six in ten people of European ancestry with Alzheimer's carry it, compared to just a quarter of the general population - implying there are more to be found.

The researchers further evaluated MGMT using multiple types of molecular data and other Alzheimer's related traits derived from human brain tissue.

Analysis showed it uses a process known as epigenetics - the code that controls our DNA.

Added senior author Professor Carole Ober, of the University of Chicago: "This study highlighted the value of founder populations for genetic mapping studies of diseases like Alzheimer's.

"The relatively uniform environment and reduced genetic variation in Hutterites increases our power to find associations in smaller sample sizes than required for studies in the general population.

"The validation of our findings in the larger dataset used by the Boston University group was enormously gratifying and ultimately led to supportive epigenetic mechanisms that connected both sets of GWAS results to the MGMT gene.”

It demonstrates the importance of searching for genetic factors for Alzheimer's that may be specific to one gender, said Dr Farrer.

Further studies are needed to understand why MGMT influences risk greater in women than men.

The results are in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer's Association.