Matches in SemOpenAlex for { <https://semopenalex.org/work/W4205650058> ?p ?o ?g. }
Showing items 1 to 71 of
71
with 100 items per page.
- W4205650058 abstract "Abstract Background Then main genetic late‐onset Alzheimer’s disease (AD) risk factor, apolipoprotein E ( APOE ) ε4 genotype is characterized by the apoE4 protein having impaired interaction with astrocyte’s ATP‐binding cassette transporter A1 (ABCA1) resulting in; (1) poor cholesterol efflux (Bielicki 2016) to apoE and reduced lipid transport to cells in brain, (2) build‐up of residual cholesterol in lipid rafts, impeding astrocyte function (Rawat 2019), and (3) increased neuron cell death (Voskuhl 2018). ApoE as opposed to most other apolipoproteins does not cross the blood brain barrier (BBB). It has been suggested that the apoA‐I subspecies preβ‐HDL effectively crosses the BBB where it can compensate for ApoE4’s impaired interaction with ABCA1. We hypothesized that the ABCA1 agonist CS6253 would generate preβ‐HDL in plasma and decrease AD risk factors in brain including Aβ42. Method In vitro : CS6253 was incubated with human plasma (Figure, A‐B) and generation of preβ‐HDL assessed by 2D electrophoreses using a.b. to apoA‐I and CS6253 generating EC50 values. In vivo : Cynomolgus monkeys (cynos) have 93% homology with human apoE, lipid and amyloid metabolism similar to humans making them representative models for humans. In cynos; (1) CS6253 single dose 25 mg/kg iv was administered (n=2) and plasma collected for preβ‐HDL analysis by ELISA (Daichii a.b.) (Figure, C); (2) CS6253 multiple dose 0 (control), 75, 150 and 225 mg/kg iv (n=2/sex/group) 5 times was administered over 10 days and plasma collected serially for preβ‐HDL analysis (Figure, D). CSF and plasma were collected before treatment and 6 hours after the 5 th /last dosing and Aβ42 and 40 analyzed by SIMOA. Result CS6253 increased preβ‐HDL in vitro in human plasma and in vivo in cynos, see Figure. In cynos CS6253 decreased Aβ42 and Aβ40 concentration in CSF following dose‐response pattern. Conclusion The CS6253 ABCA1 agonist transiently increases plasma preβ‐HDL and reduces CSF concentrations of Aβ42 and Aβ40. The Aβ reduction is consistent with apoE targeted replacement mice models studies where CS6253 reduced Aβ42, prevented AD brain pathology and improved cognition. Studies in human APOE ε4 carriers with and without AD are needed to corroborate these findings and to investigate the therapeutic potential of CS6253 or similar compounds." @default.
- W4205650058 created "2022-01-26" @default.
- W4205650058 creator A5049682377 @default.
- W4205650058 date "2021-12-01" @default.
- W4205650058 modified "2023-10-17" @default.
- W4205650058 title "CS6253 ABCA1 agonist in cynomolgus monkeys increases APOA‐I subspecies PREβ‐HDL and lowers Aβ42 and Aβ40 in cerebrospinal fluid" @default.
- W4205650058 doi "https://doi.org/10.1002/alz.056218" @default.
- W4205650058 hasPublicationYear "2021" @default.
- W4205650058 type Work @default.
- W4205650058 citedByCount "0" @default.
- W4205650058 crossrefType "journal-article" @default.
- W4205650058 hasAuthorship W4205650058A5049682377 @default.
- W4205650058 hasBestOaLocation W42056500581 @default.
- W4205650058 hasConcept C104317684 @default.
- W4205650058 hasConcept C126322002 @default.
- W4205650058 hasConcept C134018914 @default.
- W4205650058 hasConcept C149011108 @default.
- W4205650058 hasConcept C170493617 @default.
- W4205650058 hasConcept C185592680 @default.
- W4205650058 hasConcept C2777542381 @default.
- W4205650058 hasConcept C2777704780 @default.
- W4205650058 hasConcept C2778163477 @default.
- W4205650058 hasConcept C2778938600 @default.
- W4205650058 hasConcept C2779134260 @default.
- W4205650058 hasConcept C2779651940 @default.
- W4205650058 hasConcept C2779982054 @default.
- W4205650058 hasConcept C529278444 @default.
- W4205650058 hasConcept C55493867 @default.
- W4205650058 hasConcept C57089818 @default.
- W4205650058 hasConcept C62746215 @default.
- W4205650058 hasConcept C71924100 @default.
- W4205650058 hasConcept C86803240 @default.
- W4205650058 hasConcept C98274493 @default.
- W4205650058 hasConceptScore W4205650058C104317684 @default.
- W4205650058 hasConceptScore W4205650058C126322002 @default.
- W4205650058 hasConceptScore W4205650058C134018914 @default.
- W4205650058 hasConceptScore W4205650058C149011108 @default.
- W4205650058 hasConceptScore W4205650058C170493617 @default.
- W4205650058 hasConceptScore W4205650058C185592680 @default.
- W4205650058 hasConceptScore W4205650058C2777542381 @default.
- W4205650058 hasConceptScore W4205650058C2777704780 @default.
- W4205650058 hasConceptScore W4205650058C2778163477 @default.
- W4205650058 hasConceptScore W4205650058C2778938600 @default.
- W4205650058 hasConceptScore W4205650058C2779134260 @default.
- W4205650058 hasConceptScore W4205650058C2779651940 @default.
- W4205650058 hasConceptScore W4205650058C2779982054 @default.
- W4205650058 hasConceptScore W4205650058C529278444 @default.
- W4205650058 hasConceptScore W4205650058C55493867 @default.
- W4205650058 hasConceptScore W4205650058C57089818 @default.
- W4205650058 hasConceptScore W4205650058C62746215 @default.
- W4205650058 hasConceptScore W4205650058C71924100 @default.
- W4205650058 hasConceptScore W4205650058C86803240 @default.
- W4205650058 hasConceptScore W4205650058C98274493 @default.
- W4205650058 hasIssue "S9" @default.
- W4205650058 hasLocation W42056500581 @default.
- W4205650058 hasOpenAccess W4205650058 @default.
- W4205650058 hasPrimaryLocation W42056500581 @default.
- W4205650058 hasRelatedWork W1973478111 @default.
- W4205650058 hasRelatedWork W2085997836 @default.
- W4205650058 hasRelatedWork W2129077731 @default.
- W4205650058 hasRelatedWork W2132339854 @default.
- W4205650058 hasRelatedWork W2332525086 @default.
- W4205650058 hasRelatedWork W2368723127 @default.
- W4205650058 hasRelatedWork W2385287026 @default.
- W4205650058 hasRelatedWork W3211288498 @default.
- W4205650058 hasRelatedWork W2481713257 @default.
- W4205650058 hasRelatedWork W3141481402 @default.
- W4205650058 hasVolume "17" @default.
- W4205650058 isParatext "false" @default.
- W4205650058 isRetracted "false" @default.
- W4205650058 workType "article" @default.