Article

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.

Centre for Research in Neurodegenerative Diseases, Department of Medicine, Department, University of Toronto, Toronto, Ontario, Canada.
Nature Genetics (Impact Factor: 29.65). 03/2007; 39(2):168-77. DOI: 10.1038/ng1943
Source: PubMed

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.

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