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

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Item Type:	Article
Title:	The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Creators Name:	Rogaeva, E., Meng, Y., Lee, J.H., Gu, Y., Kawarai, T., Zou, F., Katayama, T., Baldwin, C.T., Cheng, R., Hasegawa, H., Chen, F., Shibata, N., Lunetta, K.L., Pardossi-Piquard, R., Bohm, C., Wakutani, Y., Cupples, L.A., Cuenco, K.T., Green, R.C., Pinessi, L., Rainero, I., Sorbi, S., Bruni, A., Duara, R., Friedland, R.P., Inzelberg, R., Hampe, W., Bujo, H., Song, Y.Q., Andersen, O.M., Willnow, T.E., Graff-Radford, N., Petersen, R.C., Dickson, D., Der, S.D., Fraser, P.E., Schmitt-Ulms, G., Younkin, S., Mayeux, R., Farrer, L.A. and St George-Hyslop, P.
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.
Keywords:	Age of Onset, Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cell Line, Cell Surface Receptors, Endosomes, Genetic Models, Genetic Variation, Haplotypes, Introns, LDL-Receptor Related Proteins, Membrane Transport Proteins, Organ Specificity, Protease Nexins, Single Nucleotide Polymorphism, Vesicular Transport Proteins
Source:	Nature Genetics
ISSN:	1061-4036
Publisher:	Nature Publishing Group
Volume:	39
Number:	2
Page Range:	168-177
Date:	February 2007
Official Publication:	https://doi.org/10.1038/ng1943
PubMed:	View item in PubMed

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