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.
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.
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