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Alzheimer’s risk gene paradoxically protects against memory loss

A new study links a variant of the apolipoprotein E gene called APOE ε4 to better memory in older age, even in the presence of amyloid plaques—a possible explanation for the variant’s persistence despite its association with an increased risk of Alzheimer’s disease.

A genetic variant previously associated with a dramatic increase in Alzheimer’s risk may protect against age- and disease-related cognitive decline, a study published in Nature Aging this week (October 7) finds.

Apolipoprotein E (APOE) is a protein involved in processing fats. A variant of this gene called APOE ε4 is the highest and most common known risk factor for Alzheimer’s. People with a single copy of the variant have three times the risk of developing the neurological disease in old age as as people with no copies, Science reports. But a 2020 study, which involved more than 1000 people aged 20 to 80, found carriers of APOE ε4 variant fared better on short term memory tests.

The new findings build on these results, Nahid Zokaei, University of Oxford psychologist and lead author of the 2020 study, tells Science, adding that the combined observations could be important in understanding the mechanism of Alzheimer’s development and how our brain works more generally.

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