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.

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease / ROGAEVA E; MENG Y; LEE JH; GU Y; KAWARAI T; ZOU F; KATAYAMA T; BALDWIN CT; CHENG; R; HASEGAWA H; CHEN F; SHIBATA N; LUNETTA KL; PARDOSSI-PIQUARD R; BOHM C; WAKUTANI Y; CUPPLES LA; CUENCO KT; GREEN RC; PINESSI L; RAINERO I; S. SORBI; BRUNI A; DUARA R; FRIEDLAND RP; INZELBERG R; HAMPE W; BUJO H; SONG YQ; ANDERSEN; OM; WILLNOW TE; GRAFF-RADFORD N; PETERSEN RC; DICKSON D; DER SD; FRASER PE; SCHMITT-ULMS G; YOUNKIN S; MAYEUX R; FARRER LA; ST GEORGE-HYSLOP P. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 39(2):(2007), pp. 168-177. [10.1038/ng1943]

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

SORBI, SANDRO;
2007

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.
2007
39(2)
168
177
ROGAEVA E; MENG Y; LEE JH; GU Y; KAWARAI T; ZOU F; KATAYAMA T; BALDWIN CT; CHENG; R; HASEGAWA H; CHEN F; SHIBATA N; LUNETTA KL; PARDOSSI-PIQUARD R; BO...espandi
File in questo prodotto:
File Dimensione Formato  
1_Nature genetics 2007.pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 360.63 kB
Formato Adobe PDF
360.63 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/307674
Citazioni
  • ???jsp.display-item.citation.pmc??? 465
  • Scopus 981
  • ???jsp.display-item.citation.isi??? 913
social impact