Understanding apolipoprotein E as a predominant cause of Alzheimer's disease.

APOE alleles account for most late-onset Alzheimer’s disease burden, with the ε3 allele increasing risk versus ε2 and ε3/ε4 together explaining the majority in populations with reliable data.

• Why it matters: The overall contribution of APOE to Alzheimer’s disease burden may be underestimated because the risk effect of the most common ε3 allele relative to ε2 is not always recognized.
• What they did: The authors synthesize epidemiological evidence across late-onset European-ancestry populations and other ethnic groups with reliable data, incorporating effects of ε3 and ε4 and considering sporadic early-onset and mutation- or trisomy 21–linked cases.
• The result: The combined evidence suggests APOE is a predominant cause spanning multiple Alzheimer’s etiologies, implying that therapies modulating APOE’s role could benefit almost all prospective Alzheimer’s cases.

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