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- Title
The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.
- Authors
Rogaeva, Ekaterina; Meng, Yan; Lee, Joseph H; Gu, Yongjun; Kawarai, Toshitaka; Zou, Fanggeng; Katayama, Taiichi; Baldwin, Clinton T; Cheng, Rong; Hasegawa, Hiroshi; Chen, Fusheng; Shibata, Nobuto; Lunetta, Kathryn L; Pardossi-Piquard, Raphaelle; Bohm, Christopher; Wakutani, Yosuke; Cupples, L Adrienne; Cuenco, Karen T; Green, Robert C; Pinessi, Lorenzo; Rainero, Innocenzo; Sorbi, Sandro; Bruni, Amalia; Duara, Ranjan; Friedland, Robert P; Inzelberg, Rivka; Hampe, Wolfgang; Bujo, Hideaki; Song, You-Qiang; Andersen, Olav M; Willnow, Thomas E; Graff-Radford, Neill; Petersen, Ronald C; Dickson, Dennis; Der, Sandy D; Fraser, Paul E; Schmitt-Ulms, Gerold; Younkin, Steven; Mayeux, Richard; Farrer, Lindsay A; St George-Hyslop, Peter
- 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.
- Publication
Nature genetics, 2007, Vol 39, Issue 2, p168
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/ng1943