@article{6c33abb7bc2b451786f558976f4347a7,
title = "The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease",
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 Β peptide (AΒ) 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 AΒ-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.",
author = "Ekaterina Rogaeva and Yan Meng and Lee, {Joseph H.} and Yongjun Gu and Toshitaka Kawarai and Fanggeng Zou and Taiichi Katayama and Baldwin, {Clinton T.} and Rong Cheng and Hiroshi Hasegawa and Fusheng Chen and Nobuto Shibata and Lunetta, {Kathryn L.} and Raphaelle Pardossi-Piquard and Christopher Bohm and Yosuke Wakutani and Cupples, {L. Adrienne} and Cuenco, {Karen T.} and Green, {Robert C.} and Lorenzo Pinessi and Innocenzo Rainero and Sandro Sorbi and Amalia Bruni and Ranjan Duara and Friedland, {Robert P.} and Rivka Inzelberg and Wolfgang Hampe and Hideaki Bujo and Song, {You Qiang} and Andersen, {Olav M.} and Willnow, {Thomas E.} and Neill Graff-Radford and Petersen, {Ronald C.} and Dennis Dickson and Der, {Sandy D.} and Fraser, {Paul E.} and Gerold Schmitt-Ulms and Steven Younkin and Richard Mayeux and Farrer, {Lindsay A.} and {St. George-Hyslop}, Peter",
note = "Funding Information: The authors thank J. Ott for advice on the statistical analysis. The authors acknowledge the work of B. Tycko, M. Medarano , R. Lantigua, Y. Stern, A. Akomolafe, J. Browndyke, H. Chui, R. Go, A. Kurz, H. Petrovitch, N. Relkin, D. Sadovnick, P. Erlich, S. Sunyaev, L. Ma, J. Lok and S. Younkin. This work was supported by the Canadian Institutes of Health Research, the Howard Hughes Medical Institute, the Canadian Institutes of Health Research– Japan Science and Technology Trust, the Alzheimer Society of Ontario, the Canada Foundation for Innovation, the Ontario Research and Development Challenge Fund, the Ontario Mental Health Foundation, Genome Canada, the US National Institutes of Health and the National Institute on Aging (grants R37-AG15473 and P01-AG07232 (R.M.), R01-AG09029 (L.A.F.), RO1-HG/ AG02213 (R.C.G.), P30-AG13846 (L.A.F., R.C.G.), R01-AG017173 (R.P.F., L.A.F.), P50-AG16574 (R.C.P., S.Y., N.G.R.) and U01-AG06786 (R.C.P.)), the Alzheimer Association, the Alzheimer Society of Canada, the Blanchett Hooker Rockefeller Foundation, the Charles S. Robertson Gift (R.M.), Fonds de la Recherche en Sant{\'e} (Y.M.), Assessorato Regionale alla Sanit{\`a}-Regione Calabria, Finalized Project of the Ministry of Health (2003–2005) (A.C.B.), Fondation pour la Recherche M{\'e}dical, Robert and Clarice Smith and Abigail Van Buren, the Alzheimer Disease Research Program (R.P., S.Y.) and the W. Garfield Weston Fellowship (E.R., G.S.U.).",
year = "2007",
month = feb,
doi = "10.1038/ng1943",
language = "English (US)",
volume = "39",
pages = "168--177",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",
}