The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. This evidence concerns the gene HLA-DRB1 and early-onset autosomal dominant Alzheimer disease.