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The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.
- Source :
-
Nature genetics [Nat Genet] 2007 Feb; Vol. 39 (2), pp. 168-77. Date of Electronic Publication: 2007 Jan 14. - Publication Year :
- 2007
-
Abstract
- The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.
- Subjects :
- Age of Onset
Amyloid beta-Peptides metabolism
Amyloid beta-Protein Precursor metabolism
Cell Line
Endosomes metabolism
Genetic Variation
Haplotypes
Humans
Introns
Models, Genetic
Organ Specificity
Polymorphism, Single Nucleotide
Protease Nexins
Receptors, Cell Surface metabolism
Vesicular Transport Proteins metabolism
Alzheimer Disease genetics
LDL-Receptor Related Proteins genetics
Membrane Transport Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1061-4036
- Volume :
- 39
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 17220890
- Full Text :
- https://doi.org/10.1038/ng1943