Science

Not All Bad? APOE4 Sharpens Memory in Older People

From the Alz Forum

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ApoE’s slight boost to working memory may explain why it has persisted in the human gene pool despite being a major risk factor for disease.

APOE4, the strongest genetic risk factor for sporadic Alzheimer’s disease, has been tied to slightly better memory in the young. Now, researchers led by Sebastian Crutch and Jonathan Schott, University College London, find a similar benefit in older people. In the October 7 Nature Aging, they reported that cognitively intact 70-year-olds carrying the APOE4 allele edged out noncarriers on a short-term visual memory task. The advantage was slight, but showed up even in people who had brain amyloid. “It was surprising that the E4 memory advantage endured in people with Aβ,” Nahid Zokaei, University of Oxford, U.K., wrote to Alzforum.

  • APOE4 carriers remembered objects and their whereabouts better than noncarriers.
  • Carriers who had brain amyloid maintained this slight edge.
  • This advantage may explain why APOE4 persists in the genome despite increasing a person’s risk of AD.

Renaud La Joie and Marianne Chapleau, University of California, San Francisco, went one further. “That they could see a cognitive benefit from APOE4 in older people is very surprising,” they said.

APOE4 increases the risk for amyloidosis and dementia (Apr 2009 newsJune 2011 newsMorris et al., 2010). Against this uncontested backdrop, some controversial research over the years has been suggesting that throughout early to mid-adulthood APOE4 carriers have a slight cognitive advantage, which then begins to wane (Rusted et al., 2013Zink et al., 2019Jochemsen et al., 2011).

To find out, first author Kirsty Lu and colleagues correlated APOE genotype, amyloid PET, structural MRI, and cognitive test data from a subset of the British 1946 Birth Cohort. These volunteers were all born during the same week after World War II and researchers have been following them ever since. Of the 398 cognitively normal participants selected for the present analysis, 30 percent carried an APOE4 allele. One-third of them also had brain amyloid, compared to just 10 percent of noncarriers.


Read the full article on the Alz Forum website – https://www.alzforum.org/news/research-news/not-all-bad-apoe4-sharpens-memory-older-people

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