PSEN1 and Alzheimer disease: Here, we provided evidence of a low frequency variant in PSEN1 gene with a significant effect on the AD risk in APOE ε4 carriers (OR = 10.7, 95% CI = 4.7–24.6) comparable only to the effect of a second APOE ε4 allele (OR = 9.9, 95% CI = 7.2.9–13.6).