SORL1 Variants in Familial Alzheimer's Disease

J Alzheimers Dis. 2018;61(4):1275-1281. doi: 10.3233/JAD-170590.


The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer's disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.

Keywords: Alzheimer’s disease; SORL1 gene; SORLA protein; familial; neurogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • LDL-Receptor Related Proteins / genetics*
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Mutation
  • Polymorphism, Single Nucleotide
  • Siblings
  • Spain


  • LDL-Receptor Related Proteins
  • Membrane Transport Proteins
  • SORL1 protein, human