Carrying two copies of the APOE-e4 variant raises the risk of Alzheimer's disease roughly 12- to 15-fold in Japanese populations, according to researchers at Niigata University - considerably less than the more than 30-fold figure that has anchored the scientific literature since the late 1990s. The team pooled data from 21 Japanese case-control studies, producing the first comprehensive reappraisal of this question in nearly three decades.
The reference point they revisited is a 1997 international meta-analysis published in JAMA by Farrer and colleagues, which reported the striking 30-fold-plus estimate for Japanese e4*4 carriers compared with people carrying the most common genotype, e3*3. That number has been repeated in papers and reviews ever since. In the years that followed, however, many more case-control studies were published in Japan, giving researchers a far larger evidence base than was available at the time.
APOE remains the strongest genetic risk factor for late-onset Alzheimer's, and a 12- to 15-fold increase is still among the largest genetic effects known for the disease. The revision matters mainly for how that risk is communicated. Genetic testing is increasingly part of research enrollment and clinical conversations, and the difference between a 30-fold and a 15-fold figure is meaningful for anyone trying to understand what a test result actually implies.
The analysis draws on Japanese case-control studies specifically, so the updated estimate speaks to that population; APOE effect sizes are known to differ across ancestral groups, which is part of why the original 1997 work reported separate figures by population in the first place.