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Long life and lower dementia risk associated with unusual gene variant


Two men sitting, focussing on an IPadPeople with a specific, unusual gene mutation seem to be protected against several dementias and to have a greater chance of longevity, an extensive international research study shows.

Anna Zettergren“These results provide further clues as to which biological mechanisms protect us against neurodegenerative diseases and improve our chances of a long life,” says Anna Zettergren, associate professor of experimental psychiatry at Sahlgrenska Academy, University of Gothenburg, one of the publication’s authors.

It was previously known that for people with an unusual variant of the PLCG2 gene, the risk for Alzheimer’s disease is half that of the population as a whole. The current findings now link this mutation with lowered risk for other neurodegenerative diseases as well, and a greater chance of living beyond age 90.

The PLCG2 protein plays an important part in the immune system, and the gene variant leads to a change in this protein that appears to affect the risks for Alzheimer’s, frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB), but not diseases like amyotrophic lateral sclerosis ALS and Parkinson’s disease.

Large, robust study

The study, published in the journal Acta Neuropathologica, is based on genetic data from several countries, including Sweden through the Gothenburg H70 Birth Cohort Studies. Altogether, these studies comprise more than 200,000 individuals, including controls.

“We’re creating the opportunity to find links to rare genetic variants by combining data from many different research groups,” says Zettergren, referring to the great scope of the study.

Three other Swedish researchers at Sahlgrenska Academy who have taken part are Kaj Blennow and Henrik Zetterberg, professors of neurochemistry, and Ingmar Skoog, a professor of psychiatry who is also the director of AgeCap, the Centre for Ageing and Health at the University of Gothenburg.

Maybe a piece of the puzzle

Research on medicinal treatment for Alzheimer’s disease has had repeated setbacks. To date, all drug studies have failed, Skoog states. However, he thinks the new discoveries confirm that the mutation in PLCG2 is a clue for further research.

Anna Zettergren“The findings warrant further study and may come to be part of the outsized jigsaw puzzle that needs completing to enable us, in the long term, to develop drugs against dementia diseases.”

Title: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

Contacts: Anna Zettergren and Ingmar Skoog

Illustrations: Genre image (photo: Mattonstock) and portrait picture of Anna Zettergren (photo: Cecilia Hedström) and Ingmar Skoog (photo: Johan Wingborg)