Just kidding, emigration won’t fix this problem. Recently, out of Iceland, came news of an amyloid precursor protein variant that protected a lucky 1 percent of the islanders from Alzheimer’s disease. Alas, far fewer Americans stand to inherit such good fortune, according to results of a multicenter study published in the February 1 JAMA Neurology. The authors found the allegedly protective alanine-673-threonine allele in just three DNA samples from nearly 20,000 American Caucasians.
“This variant is extremely rare and does not have a discernible impact on AD risk in the U.S. population,” concluded the authors, led by Gerard Schellenberg of the University of Pennsylvania School of Medicine in Philadelphia.
The mutation sits next to APP’s cleavage site for BACE1 and suppresses Aβ production. Even in Iceland, the A673T substitution is rare, but the original study authors reported it was five times more prevalent in elderly people without dementia than in those with AD. Those researchers also detected the variant in nearly one in 100 people in Scandinavian countries, but only one in 5,000 North Americans (see Jul 2012 news). In a different study of North Americans, the variant was a no-show in more than 4,000 people (Bamne et al., 2014).
In the new work, Schellenberg and colleagues picked up the variant in two of 10,480 cognitively normal Americans—one of whom hailed from Iceland—and one of 8,943 people with AD. That person was 89 when AD symptoms began, which is consistent with the allele being protective. The authors also examined DNA from 1,569 Swedes, and found three instances of the variant, all in controls. This is similar to the frequency reported earlier in that population.
The present cohort was big enough to determine that A673T occurs only rarely in Americans, commented Rita Guerreiro of University College London, who was not involved in the work (see full comment below). However, given just how rarely A673T turns up, she believes the study was still too small to confirm or rule out that the variant indeed protects against dementia.
What about other populations? A community study of 515 citizens of Vantaa, Finland, captured just one instance of A673T, in a woman who died at the age of 104 with no signs of AD (see Mar 2013 news). Two studies encompassing more than 11,000 Chinese people failed to find a single A673T allele (Ting et al., 2013; Liu et al., 2014). “This variant may be primarily restricted to Icelandic and Scandinavian populations,” wrote Schellenberg and colleagues. Philippe Amouyel of the Institute Pasteur de Lille in France, who is also investigating A673T in European samples, told Alzforum in an email that his data also indicate the mutation may be limited to certain populations.—Amber Dance
- Protective APP Mutation Found—Supports Amyloid Hypothesis
- In Shout-Out for Community Studies, Vantaa Finds Protective Mutation
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