Alzheimer’s risk gene has potential cognitive benefits

UCL scientists have found that people with the Alzheimer’s risk gene, APOE4, perform better in visual working memory tests than people without the gene.

The most studied gene with the largest effect on our Alzheimer’s risk is called APOE. Everyone has two copies of the APOE gene. There are 3 versions of the gene (E2, E3, E4) and people who inherit one copy of the APOE E4 version (roughly one in four people) are around three times more likely to develop Alzheimer’s disease, compared to people without this version of the gene. Those with two copies may be more than eight times more likely to develop Alzheimer’s.

The UCL team led by Dr Kirsty Lu, Prof Seb Crutch and Prof Jonathan Schott worked with a unique group of nearly 400 volunteers, recruited from the Medical Research Council National Survey of Health and Development (NSHD) 1946 British Birth Cohort. They were all born in the same week in 1946 and did not have dementia. The findings are published in the scientific journal Nature Aging.

The team assessed the effects of the APOE4 risk gene, and b-amyloid – one of the hallmark Alzheimer’s proteins – as measured by a PET brain scan, on visual working memory.

They found having the APOE4 gene and the presence of b-amyloid in the brain had opposing effects on object identification, with APOE4 predicting better recall and amyloid build-up predicting poorer recall. APOE4 carriers were also able to recall locations more precisely.

The results, suggesting better visual working memory in those with APOE4, suggests that there are some benefits of this gene in the older age, and even when proteins associated with Alzheimer’s disease are building up.

Prof Schott said: “We have long known that possession of an APOE4 risk gene increases risk for Alzheimer’s disease,, but the exact mechanism by which it does so remains uncertain. Our finding – from a sample of individuals from across mainland Britain who were all born in the same week in 1946 – that carrying an APOE4 gene was associated with better visual memory may provide clues to why this gene variant is so common. Understanding why APOE4 might result in better memory, may also help us to understand why it also leads to increased risk for Alzheimer’s disease”

Dr Kirsty Lu of UCL, first author on the study, said: “Previous evidence has suggested that the APOE4 gene is one of various genetic variants that cause harm late in life, but may confer benefits earlier in life, during or before reproductive years. Here we have found that APOE4’s benefits may in fact persist into old age, at the same time that the harms of Alzheimer’s disease are beginning to develop.”

Image: Photo 99185027 © Atthapon Raksthaput |