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• W3178486483 abstract "Cerebrovascular dysfunction is a hallmark feature of Alzheimer's disease (AD). One of the greatest risk factors for AD is the apolipoprotein E4 (E4) allele. The APOE4 genotype has been shown to negatively impact vascular amyloid clearance, however, its direct influence on the molecular integrity of the cerebrovasculature compared to other APOE variants (APOE2 and APOE3) has been largely unexplored. To address this, we employed a 10-plex tandem isobaric mass tag approach in combination with an ultra-high pressure liquid chromatography MS/MS (Q-Exactive) method, to interrogate unbiased proteomic changes in cerebrovessels from AD and healthy control brains with different APOE genotypes. We first interrogated changes between healthy control cases to identify underlying genotype specific effects in cerebrovessels. EIF2 signaling, regulation of eIF4 and 70S6K signaling and mTOR signaling were the top significantly altered pathways in E4/E4 compared to E3/E3 cases. Oxidative phosphorylation, EIF2 signaling and mitochondrial dysfunction were the top significant pathways in E2E2 vs E3/E3cases. We also identified AD-dependent changes and their interactions with APOE genotype and found the highest number of significant proteins from this interaction was observed in the E3/E4 (192) and E4/E4 (189) cases. As above, EIF2, mTOR signaling and eIF4 and 70S6K signaling were the top three significantly altered pathways in E4 allele carriers (i.e. E3/E4 and E4/E4 genotypes). Of all the cerebrovascular cell-type specific markers identified in our proteomic analyses, endothelial cell, astrocyte, and smooth muscle cell specific protein markers were significantly altered in E3/E4 cases, while endothelial cells and astrocyte specific protein markers were altered in E4/E4 cases. These proteomic changes provide novel insights into the longstanding link between APOE4 and cerebrovascular dysfunction, implicating a role for impaired autophagy, ER stress, and mitochondrial bioenergetics. These APOE4 dependent changes we identified could provide novel cerebrovascular targets for developing disease modifying strategies to mitigate the effects of APOE4 genotype on AD pathogenesis." @default.
• W3178486483 created "2021-07-19" @default.
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• W3178486483 date "2021-07-08" @default.
• W3178486483 modified "2023-10-15" @default.
• W3178486483 title "APOE genotype dependent molecular abnormalities in the cerebrovasculature of Alzheimer’s disease and age-matched non-demented brains" @default.
• W3178486483 cites W1018991385 @default.
• W3178486483 cites W1147956078 @default.
• W3178486483 cites W1522806115 @default.
• W3178486483 cites W1566253016 @default.
• W3178486483 cites W1603244154 @default.
• W3178486483 cites W1616122655 @default.
• W3178486483 cites W1671478575 @default.
• W3178486483 cites W1870043354 @default.
• W3178486483 cites W1968954730 @default.
• W3178486483 cites W1978873309 @default.
• W3178486483 cites W1980001884 @default.
• W3178486483 cites W1982206682 @default.
• W3178486483 cites W1993014997 @default.
• W3178486483 cites W1995118675 @default.
• W3178486483 cites W2001462666 @default.
• W3178486483 cites W2002589314 @default.
• W3178486483 cites W2004063915 @default.
• W3178486483 cites W2011640156 @default.
• W3178486483 cites W2014013095 @default.
• W3178486483 cites W2020240430 @default.
• W3178486483 cites W2023426214 @default.
• W3178486483 cites W2023649381 @default.
• W3178486483 cites W2024353040 @default.
• W3178486483 cites W2030443908 @default.
• W3178486483 cites W2031762899 @default.
• W3178486483 cites W2032453195 @default.
• W3178486483 cites W2036661577 @default.
• W3178486483 cites W2043209737 @default.
• W3178486483 cites W2043385504 @default.
• W3178486483 cites W2045463471 @default.
• W3178486483 cites W2046985190 @default.
• W3178486483 cites W2049881362 @default.
• W3178486483 cites W2052100826 @default.
• W3178486483 cites W2053005839 @default.
• W3178486483 cites W2053091943 @default.
• W3178486483 cites W2054931992 @default.
• W3178486483 cites W2055467683 @default.
• W3178486483 cites W2056205328 @default.
• W3178486483 cites W2060972192 @default.
• W3178486483 cites W2065366704 @default.
• W3178486483 cites W2067655381 @default.
• W3178486483 cites W2068216402 @default.
• W3178486483 cites W2069121057 @default.
• W3178486483 cites W2070716601 @default.
• W3178486483 cites W2076215149 @default.
• W3178486483 cites W2077518473 @default.
• W3178486483 cites W2079090326 @default.
• W3178486483 cites W2079975961 @default.
• W3178486483 cites W2086363884 @default.
• W3178486483 cites W2087529125 @default.
• W3178486483 cites W2094738952 @default.
• W3178486483 cites W2096142564 @default.
• W3178486483 cites W2104346169 @default.
• W3178486483 cites W2107281222 @default.
• W3178486483 cites W2107680694 @default.
• W3178486483 cites W2115403312 @default.
• W3178486483 cites W2117130548 @default.
• W3178486483 cites W2117543363 @default.
• W3178486483 cites W2121101037 @default.
• W3178486483 cites W2123001830 @default.
• W3178486483 cites W2134563219 @default.
• W3178486483 cites W2135581618 @default.
• W3178486483 cites W2138992210 @default.
• W3178486483 cites W2140425743 @default.
• W3178486483 cites W2140718540 @default.
• W3178486483 cites W2142803335 @default.
• W3178486483 cites W2145838320 @default.
• W3178486483 cites W2146653387 @default.
• W3178486483 cites W2149801164 @default.
• W3178486483 cites W2152426966 @default.
• W3178486483 cites W2159899308 @default.
• W3178486483 cites W2162143298 @default.
• W3178486483 cites W2167597327 @default.
• W3178486483 cites W2283957277 @default.
• W3178486483 cites W2416710009 @default.
• W3178486483 cites W2471768729 @default.
• W3178486483 cites W2473518066 @default.
• W3178486483 cites W2515949854 @default.
• W3178486483 cites W2617019071 @default.
• W3178486483 cites W2754890392 @default.
• W3178486483 cites W2756959977 @default.
• W3178486483 cites W2784098514 @default.
• W3178486483 cites W2790758778 @default.

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