NIA-funded research on the APOE gene suggests that the APOE ε2 allele may confer protection against Alzheimer’s disease. The APOE gene encompasses three different versions, or alleles: ε2, ε3, and ε4. The ε2 allele is the rarest and is associated with decreased AD risk; the ε3 allele is the most common and appears to neither increase or decrease AD risk; and the less common ε4 allele is associated with increased AD risk. Researchers in the current investigation aimed to clarify the precise role of APOE ε2 in AD risk. They calculated risk estimates based on data from over 5,000 autopsy-confirmed AD cases and controls from the NIA-funded Alzheimer’s Disease Genetics Consortium (ADGC). Of the 5,000+ cases, only 24 individuals had two copies of APOE ε2, but these individuals showed a 66% reduction in AD risk compared with ε2/ε3 carriers; an 87% risk reduction compared with ε3/ε3 carriers; and a 99% risk reduction compared with ε4/ε4 carriers. In an additional ADGC sample, ε2/ε2 carriers again showed decreased AD risk. These results point towards an opportunity to elucidate the molecular mechanisms through which APOE ε2 lowers AD risk, which could in turn assist in the development of broader AD treatment and prevention strategies. This study was published in Nature Communications.