The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate some of the main findings.<h4>Results</h4>Higher plasma PCSK9 protein levels were associated with a lower risk of AD (HR [95%CI]: 0.74 [0.58, 0.94]; <i>p</i> = 0.01) in <i>APOE</i> ε4 noncarriers; in contrast, PCSK9 levels were not significantly associated with AD risk in <i>APOE</i> ε4 carriers, after adjusting for common confounders, lipid profile, and lipid treatment. This evidence concerns the gene PCSK9 and early-onset autosomal dominant Alzheimer disease.