Study finds gene that protect against Alzheimer’s & Parkinson’s

NEW YORK — People with a particular version of a gene involved in immune response had a lower risk of Alzheimer’s and Parkinson’s disease, according to a massive study of medical and genetic data.

The protective gene version, or allele identified in the study, published online in the Proceedings of the National Academy of Sciences, is called DR4, and is carried by about one in every five people.

Researchers from the Stanford University in the US found that people with DR4 had reduced chances of contracting either Parkinson’s or Alzheimer’s by more than 10 per cent on average.

These lucky people may someday benefit all the more from a vaccine that could slow or stall the progression of these two most common neurodegenerative conditions.

“In an earlier study we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” said Emmanuel Mignot, Professor in Sleep Medicine, psychiatry and behavioural sciences from Stanford Medicine.

“Now, we’ve found a similar impact of DR4 on Alzheimer’s disease,” he added.

In the study, the team included more than 100,000 people with Alzheimer’s disease and more than 40,000 with Parkinson’s disease from Europe, East Asia, the Middle East, and South and North America.

The investigators also analysed data from the autopsied brains of more than 7,000 Alzheimer’s patients and found that DR4 carriers had fewer neurofibrillary tangles — long, filamentous aggregates, composed largely of tau, that characterise Alzheimer’s disease — as well as a later onset of symptoms, than their non-DR4 counterparts.

The presence of neurofibrillary tangles has been shown to correlate strongly with the condition’s severity.

Carrying DR4 also correlated with a later onset of symptoms in Parkinson’s patients, even though neurofibrillary tangles aren’t typically seen in that disease.

This study hints that tau, an essential player in Alzheimer’s, may turn out to also play some kind of role in Parkinson’s, Mignot said, although what that role may be is not clear.

Noting DR4’s beneficial effects on tau levels and pathologies in both Alzheimer’s and Parkinson’s, the researchers zeroed in on tau.

They chopped molecules of the protein into 482 peptides collectively spanning tau’s entire sequence, then placed them into separate dishes along with DR4’s protein product (also called DR4) to see if it binds strongly to any of those peptides.

In addition, the researchers tested all the biologically likely chemical modifications each of those peptides can accrue once it’s been produced inside a cell.

In people who carry any of the protective variants of DR4 (not all of them are protective) and whose brains have begun to accumulate tau aggregates, a vaccine could delay onset or slow progression of Alzheimer’s and possibly Parkinson’s, Mignot suggested.

People who don’t carry DR4 wouldn’t benefit from this vaccine, Mignot noted.

A blood test ought to be given to see who should or shouldn’t get vaccinated, Mignot said.

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