Researchers shed new light on the genetics of memory performance

A/Prof Srikanth

In the largest study of the genetics of memory ever undertaken, an international research team including scientists from the School of Clinical Sciences at Monash Health (SCS) has discovered two common genetic variants believed to be associated with memory performance.

Published last week in Biological Psychiatry, the findings are a significant step towards better understanding how memory loss is inherited.

Longer life spans and the increased prevalence of memory impairment and dementia world-wide underscore the critical public health importance of efforts aimed at deciphering the underlying mechanisms of human memory.  

The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium was developed to facilitate the study of the entire genome through pooling of data from research centers all across the world. Nearly 30,000 participants who did not have dementia were included in the study. Each participant completed memory tests, such as word recall, and their entire genome was genotyped. Using sophisticated statistical analysis, the genome was examined for segments that were associated with low memory scores.

Funded by the National Health and Medical Research Council (NHMRC), Head of Stroke and Ageing Research at SCS Associate Professor Velandai Srikanth and his team of Australian collaborators contributed to this analysis and report using data from the Tasmanian Study of Cognition and Gait (TASCOG).

"It is exciting to contribute to such a large international collaboration, which offers great opportunities towards understanding mechanisms involved in brain ageing and dementia,” said Associate Professor Srikanth.

“Ultimately the knowledge derived from these studies will assist in efforts to preserve brain health in ageing individuals and offset the risk of dementia."

The researchers found genetic variants near the Apolipoprotein E gene, known to harbor an increased risk of dementia (especially Alzheimer disease), were associated with poorer memory performance, mostly so in the oldest participants and for the short story recall.

In a sub-study with post-mortem brain samples, participants with an increasing load of memory risk variants also had more pathological features of Alzheimer disease, perhaps reflecting in some instances early pre-clinical stages of the disease.

According to the researchers two additional regions of the genome, pointing to genes involved in immune response, were associated with the ability to recall word lists, providing new support for an important role of immune system dysfunction in age-related memory decline.

“Interestingly genetic variants associated with memory performance also predicted altered levels of expression of certain genes in the hippocampus, a key region of the brain for the consolidation of information,” explained lead author Stéphanie Debette, MD, PhD, adjunct Associate Professor of neurology at Boston University School of Medicine (BUSM).

“These were mainly genes involved in the metabolism of ubiquitin that plays a pivotal role in protein degradation.”

This unprecedented world-wide collaboration has generated novel important hypotheses on the biological underpinnings of memory decline in old age, however the researchers caution that more research is clearly needed to confirm these findings.