Alzheimer's Risk Gene APOE4 Could Be Associated with Better Visual Working Memory

Article: Potential cognitive benefits of major Alzheimer’s risk gene 
Source: University College London (U.K.)
Published: October 7, 2021 

To date, scientists have found versions of at least 30 different genes associated with an altered risk of developing Alzheimer's disease, the most common cause of dementia. Of these, the gene APOE, which encodes apolipoprotein E, has the largest effect on Alzheimer's disease risk. APOE  comes in three variants (E2, E3, and E4), and each of us carries two copies of this gene, one from each parent. Individuals who inherit one copy of the E4 version of APOE  (approximately 25% of people) are roughly three times more likely to develop Alzheimer’s disease compared to those who do not carry the E4 version. Individuals with two copies of the E4 version are more than eight times more likely to develop Alzheimer's disease. It is curious, then, that some individuals who possess the APOE4  risk gene demonstrate better performance in visual working memory. Researchers in the U.K. studied 400 volunteers from the Medical Research Council National Survey of Health and Development (NSHD) 1946 British Birth Cohort, this cohort being characterized by being born in the same week in 1946. The researchers assessed the effects of the APOE4  risk gene and beta-amyloid (a hallmark of Alzheimer's disease), as measured by a brain PET scan, on visual working memory, which was measured using a computerized "What was where?" task (recalling identities and locations). The findings showed that having the APOE4  gene and the presence of beta-amyloid in the brain had opposing effects on object identification, with APOE4  predicting better recall (and more precise location recall) and amyloid build-up predicting poorer recall. This suggests that having a copy of the APOE4  gene could confer some benefits in older age, even in the presence of amyloid plaques, and could provide clues as to why this gene variant is so common. Some earlier studies point to APOE4  conferring some benefits in younger age; the researchers suggest that this benefit could persist into older age. Although the connection might be of little comfort to patients living with Alzheimer's, building a more complete picture of the disease, such as why APOE4  might result in better memory, may also help us to understand why it also leads to increased risk for Alzheimer’s.

My rating of this study: ⭐⭐🌸

Lu K, Nicholas JM, Pertzov Y, et al. "Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory." Nature Aging.  1:1002-1009. 7 October 2021. https://doi.org/10.1038/s43587-021-00117-4