Implication of Sex and SORL1 Variants in Italian Patients With Alzheimer Disease

Abstract

Multiple susceptibility genes have been implicated as possible risk factors for late-onset Alzheimer disease (LOAD), but only the apolipoprotein E (APOE; NCBI Entrez Gene NM_000041.2) ε4 allele is recognized worldwide as a major contributor to the disease. Recently, sortilin-related receptor (SORL1; NCBI Entrez Gene NM_003105.4) has been proposed as another important genetic candidate for LOAD.¹SORL1 is involved in intracellular trafficking and recycling the amyloid β (Aβ) peptide into the endocytic pathway.¹ Patients with Alzheimer disease (AD) have lower SORL1 expression levels, whereas SORL1 knockout animal models present increased brain Aβ levels, suggesting that SORL1 has an inhibiting effect on the Aβ protein precursor amyloidogenic pathways.^2,3