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Alzheimer's risk gene variant protects against age-related memory loss

18 October 2021
Appeared in BioNews 1117

A gene variant previously linked to higher Alzheimer's risk may in fact improve short-term memory, researchers have found.

Research at University College London (UCL) has shown that the gene variant APOE4 is associated with better short-term memory. The potentially controversial findings may explain why the variant has survived in the population, despite being strongly associated with an increased risk of Alzheimer's.

'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,' explained joint senior author Professor Jonathan Schott at UCL. 'Our finding... that carrying an APOE4 gene was associated with better visual memory may provide clues to why this gene variant is so common'.

The study, published in Nature Ageing, focused on 398 participants aged between 69 and 71 who had not been diagnosed with neurological disease. The team used neuroimaging to assess for beta-amyloid plaques in the brains of participants – these form when amyloid proteins accumulate and indicate early Alzheimer's disease. Participants were then tasked with a computer-based visual memory test, which asked them to remember the identity and location of objects flashed on a screen. 

The researchers found that subjects with at least one copy of the APOE4 gene variant were 14 percent less likely to make mistakes when identifying objects, and could recall their location with seven percent more precision than non-carriers of APOE4. In addition, in participants with more abundant beta-amyloid plaques, APOE4 conferred an even stronger advantage on visual memory tests. 

'It is striking that the cognitive advantage [from APOE4] is observed even in the presence of Alzheimer's pathology,' commented Professor Duke Han, neuropsychologist at the University of Southern California, who was not involved in the study.

However, while APOE4 carriers also fared better on some verbal tests, they ultimately performed less well on long-term memory tasks.

The APOE gene codes for the protein apolipoprotein E, which is involved in fat metabolism. There are three variants in the population, but those who carry at least one copy of the APOE4 variant are 3-12 times more likely to develop Alzheimer's. 

The findings are paradoxical to APOE4's role as an Alzheimer's risk factor. The authors therefore cautioned that more research is needed in order to determine a possible protective function of APOE4.

Dr Susan Kohlhaas, director of research at Alzheimer's Research UK, which funded the study, said: 'This new research highlights that there is still a lot to be understood about these genes, their role in the development of Alzheimer's, and intriguingly what effects they may have beyond the disease.'

Alzheimer's risk gene paradoxically protects against memory loss
The Scientist |  8 October 2021
Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory
Nature Ageing |  7 October 2021
Potential cognitive benefits of major Alzheimer's risk gene
University College London |  7 October 2021
The most common Alzheimer's risk gene may also protect against memory loss
Science |  7 October 2021
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