Медицинская библиотека · Nature genetics · 2007

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

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

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Аннотация

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.

Для цитирования: 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. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.. Nature genetics. 2007. DOI: 10.1038/ng1943.

Предметные рубрики MeSH

Age of Onset Alzheimer Disease Amyloid beta-Peptides Amyloid beta-Protein Precursor Cell Line Endosomes Genetic Variation Haplotypes Humans Introns LDL-Receptor Related Proteins Membrane Transport Proteins Models, Genetic Organ Specificity Polymorphism, Single Nucleotide Protease Nexins Receptors, Cell Surface Vesicular Transport Proteins

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