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

Item Type:Article
Title:The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease
Creators Name:Rogaeva, E. and Meng, Y. and Lee, J.H. and Gu, Y. and Kawarai, T. and Zou, F. and Katayama, T. and Baldwin, C.T. and Cheng, R. and Hasegawa, H. and Chen, F. and Shibata, N. and Lunetta, K.L. and Pardossi-Piquard, R. and Bohm, C. and Wakutani, Y. and Cupples, L.A. and Cuenco, K.T. and Green, R.C. and Pinessi, L. and Rainero, I. and Sorbi, S. and Bruni, A. and Duara, R. and Friedland, R.P. and Inzelberg, R. and Hampe, W. and Bujo, H. and Song, Y.Q. and Andersen, O.M. and Willnow, T.E. and Graff-Radford, N. and Petersen, R.C. and Dickson, D. and Der, S.D. and Fraser, P.E. and Schmitt-Ulms, G. and Younkin, S. and Mayeux, R. and 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 (U.S.A.)
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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