SORL1 mutations in early- and late-onset Alzheimer disease.

ABSTRACT:

Objective

To characterize the clinical and molecular effect of mutations in the sortilin-related receptor (SORL1) gene.

Methods

We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants. The phenotypic consequences associated with SORL1 mutations were characterized based on clinical reviews of medical records. Functional studies were completed to evaluate β-amyloid (Aβ) production and amyloid precursor protein (APP) trafficking associated with SORL1 mutations.

Results

SORL1 alterations were present in 2 EOAD families. In one, a SORL1 T588I change was identified in 4 individuals with AD, 2 of whom had parkinsonian features. In

SUBMITTER: Cuccaro ML 

PROVIDER: S-EPMC5082932 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature