These findings were validated by the ADNI study, which showed that the PCSK9 genotypes were associated with AD risk and with the AD biomarker-a low concentration of Aβ42 in CSF, only in APOE ε4 noncarriers.<h4>Conclusions</h4>Our study suggests that high blood PCSK9 levels are protective against AD risk in <i>APOE</i> ε4 noncarriers, potentially through mechanisms related to lipid metabolism. The gene discussed is PCSK9; the disease is Alzheimer disease.