The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease.

TitleThe neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2008
AuthorsLee, JH, Barral, S, Reitz, C
JournalCurr Neurol Neurosci Rep
Volume8
Issue5
Pagination384-91
Date Published2008 Sep
ISSN1534-6293
KeywordsAge of Onset, Aged, Alleles, Alzheimer Disease, Amyloid beta-Protein Precursor, Chromosome Mapping, Endosomes, Gene Expression Profiling, Genetic Predisposition to Disease, Haplotypes, Humans, LDL-Receptor Related Proteins, Membrane Transport Proteins, Polymorphism, Single Nucleotide, Protein Transport, Risk, trans-Golgi Network
Abstract

Recent studies indicate that two clusters of single nucleotide polymorphisms in the neuronal sortilin-related receptor gene (SORL1) are causally associated with late-onset Alzheimer's disease (AD). At the cellular level, SORL1 is thought to be involved in intracellular trafficking of amyloid precursor protein. When this gene is suppressed, toxic amyloid beta production is increased, and high levels of amyloid betaare associated with a higher AD risk. Extending the cellular findings, gene expression studies show that SORL1 is differentially expressed in AD patients compared with controls. Furthermore, several genetic studies have identified allelic and haplotypic SORL1 variants associated with late-onset AD, and these variants confer small to modest risk of AD. Taken together, the evidence for SORL1 as a causative gene is compelling. However, putative variants have not yet been identified. Further research is necessary to determine its utility as a diagnostic marker of AD or as a target for new therapeutic approaches.

Alternate JournalCurr Neurol Neurosci Rep
PubMed ID18713574
PubMed Central IDPMC2694663
Grant ListP01 AG007232-20 / AG / NIA NIH HHS / United States
P50-AG08702 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
P01-AG07232 / AG / NIA NIH HHS / United States
P50 AG008702-19 / AG / NIA NIH HHS / United States
P01 AG007232 / AG / NIA NIH HHS / United States
R37 AG015473-11 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
R37 AG15473 / AG / NIA NIH HHS / United States