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- W4322020153 abstract "Summary SORL1 is strongly implicated in the pathogenesis of Alzheimer’s disease (AD) through human genetic studies that point to an association of reduced SORL1 levels with higher risk for AD. To interrogate the role(s) of SORL1 in human brain cells, SORL1 null iPSCs were generated, followed by differentiation to neuron, astrocyte, microglia, and endothelial cell fates. Loss of SORL1 led to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. Intriguingly, SORL1 loss led to a dramatic neuron-specific reduction in APOE levels. Further, analyses of iPSCs derived from a human aging cohort revealed a neuron-specific linear correlation between SORL1 and APOE RNA and protein levels, a finding validated in human post-mortem brain. Pathway analysis implicated intracellular transport pathways and TGF- β/SMAD signaling in the function of SORL1 in neurons. In accord, enhancement of retromer-mediated trafficking and autophagy rescued elevated phospho-tau observed in SORL1 null neurons but did not rescue APOE levels, suggesting that these phenotypes are separable. Stimulation and inhibition of SMAD signaling modulated APOE RNA levels in a SORL1-dependent manner. These studies provide a mechanistic link between two of the strongest genetic risk factors for AD." @default.
- W4322020153 created "2023-02-26" @default.
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- W4322020153 date "2023-02-25" @default.
- W4322020153 modified "2023-09-30" @default.
- W4322020153 title "Cell-type-specific regulation of APOE levels in human neurons by the Alzheimer’s disease risk gene SORL1" @default.
- W4322020153 cites W1459719961 @default.
- W4322020153 cites W1965758080 @default.
- W4322020153 cites W1967519462 @default.
- W4322020153 cites W1970706179 @default.
- W4322020153 cites W1977570151 @default.
- W4322020153 cites W1984544042 @default.
- W4322020153 cites W1988983557 @default.
- W4322020153 cites W1996675875 @default.
- W4322020153 cites W2001726213 @default.
- W4322020153 cites W2006409771 @default.
- W4322020153 cites W2012894757 @default.
- W4322020153 cites W2016590297 @default.
- W4322020153 cites W2016683781 @default.
- W4322020153 cites W2021919788 @default.
- W4322020153 cites W2032822445 @default.
- W4322020153 cites W2033318657 @default.
- W4322020153 cites W2034171109 @default.
- W4322020153 cites W2040027262 @default.
- W4322020153 cites W2042421739 @default.
- W4322020153 cites W2042883482 @default.
- W4322020153 cites W2050638819 @default.
- W4322020153 cites W2051421801 @default.
- W4322020153 cites W2058880763 @default.
- W4322020153 cites W2058888442 @default.
- W4322020153 cites W2069970378 @default.
- W4322020153 cites W2072408699 @default.
- W4322020153 cites W2083020365 @default.
- W4322020153 cites W2090139525 @default.
- W4322020153 cites W2115040576 @default.
- W4322020153 cites W2115779804 @default.
- W4322020153 cites W2119487442 @default.
- W4322020153 cites W2121349242 @default.
- W4322020153 cites W2123056267 @default.
- W4322020153 cites W2131108668 @default.
- W4322020153 cites W2132040133 @default.
- W4322020153 cites W2132590722 @default.
- W4322020153 cites W2141859364 @default.
- W4322020153 cites W2142306178 @default.
- W4322020153 cites W2143955562 @default.
- W4322020153 cites W2150022733 @default.
- W4322020153 cites W2170551349 @default.
- W4322020153 cites W2171808845 @default.
- W4322020153 cites W2287365612 @default.
- W4322020153 cites W2323326409 @default.
- W4322020153 cites W2325841306 @default.
- W4322020153 cites W2481611869 @default.
- W4322020153 cites W2520459152 @default.
- W4322020153 cites W2544929416 @default.
- W4322020153 cites W2551025035 @default.
- W4322020153 cites W2568317134 @default.
- W4322020153 cites W2605401453 @default.
- W4322020153 cites W2620116489 @default.
- W4322020153 cites W2622665060 @default.
- W4322020153 cites W2756959977 @default.
- W4322020153 cites W2768408354 @default.
- W4322020153 cites W2775642640 @default.
- W4322020153 cites W2789397833 @default.
- W4322020153 cites W2790644409 @default.
- W4322020153 cites W2791403874 @default.
- W4322020153 cites W2792014903 @default.
- W4322020153 cites W2798230823 @default.
- W4322020153 cites W2805798400 @default.
- W4322020153 cites W2809330972 @default.
- W4322020153 cites W2887980327 @default.
- W4322020153 cites W2899406479 @default.
- W4322020153 cites W2905656859 @default.
- W4322020153 cites W2916749909 @default.
- W4322020153 cites W2941381527 @default.
- W4322020153 cites W2942678593 @default.
- W4322020153 cites W2951968424 @default.
- W4322020153 cites W2953383090 @default.
- W4322020153 cites W2956173529 @default.
- W4322020153 cites W2995298326 @default.
- W4322020153 cites W3005901855 @default.
- W4322020153 cites W3029808235 @default.
- W4322020153 cites W3088072832 @default.
- W4322020153 cites W3093903285 @default.