The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimerʼs disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimerʼs disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤ 1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR) = 5.03, 95% confidence interval (CI) = (2.02-14.99), P = 7.49.10). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR = 8.86, 95% CI = (3.35-27.31), P = 3.82.10). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.