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- W1978284384 abstract "Sorting mechanisms that cause the amyloid precursor protein (APP) and the β- and γ-secretases to colocalize in the same compartment play an important role in the regulation of Aβ production in Alzheimer's disease (AD). We and several groups have reported that genetic variants in the Sortilin-related receptor (SORL1) increased the risk of AD, that SORL1 is involved in trafficking of APP, and that under-expression of SORL1 leads to over-production of Aβ. We now explored the role of one of its homologues, the sortilin-related VPS10 domain containing receptor 1 (SORCS1), in AD. We analyzed the genetic associations between AD and 16 SORCS1-SNPs in six independent data sets (2809 cases and 3482 controls). In addition, we compared SORCS1 expression levels of affected and unaffected brain regions in AD and control brains in microarray gene expression and RT-PCR sets, explored the effects of significant SORCS1-SNPs on SORCS1 brain expression levels, and explored the effect of suppression and over expression of the common SORCS1 isoforms on APP processing and Aβ generation. Inherited variants in SORCS1 were associated with AD in all datasets (0.001 < p < 0.049). In addition, SorCS1 influenced APP processing. While over expression of SorCS1 reduced γ-secretase activity and Aβ levels, the suppression of SorCS1 increased γ-secretase processing of APP and the levels of Aβ. These data suggest that inherited or acquired changes in SORCS1 expression or function may play a role in the pathogenesis of AD." @default.
- W1978284384 created "2016-06-24" @default.
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- W1978284384 date "2010-07-01" @default.
- W1978284384 modified "2023-10-18" @default.
- W1978284384 title "P4‐031: Sorcs1 Alters APP Processing and Variants may Increase Alzheimer's Disease Risk" @default.
- W1978284384 doi "https://doi.org/10.1016/j.jalz.2010.08.091" @default.
- W1978284384 hasPublicationYear "2010" @default.
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