FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3157473458> ?p ?o ?g. }

• W3157473458 abstract "Passive immunotherapies targeting Aβ continue to be evaluated as Alzheimer's disease (AD) therapeutics, but there remains debate over the mechanisms by which these immunotherapies work. Besides the amount of preexisting Aβ deposition and the type of deposit (compact or diffuse), there is little data concerning what factors, independent of those intrinsic to the antibody, might influence efficacy. Here we (i) explored how constitutive priming of the underlying innate activation states by Il10 and Il6 might influence passive Aβ immunotherapy and (ii) evaluated transcriptomic data generated in the AMP-AD initiative to inform how these two cytokines and their receptors' mRNA levels are altered in human AD and an APP mouse model.rAAV2/1 encoding EGFP, Il6 or Il10 were delivered by somatic brain transgenesis to neonatal (P0) TgCRND8 APP mice. Then, at 2 months of age, the mice were treated bi-weekly with a high-affinity anti-Aβ1-16 mAb5 monoclonal antibody or control mouse IgG until 6 months of age. rAAV mediated transgene expression, amyloid accumulation, Aβ levels and gliosis were assessed. Extensive transcriptomic data was used to evaluate the mRNA expression levels of IL10 and IL6 and their receptors in the postmortem human AD temporal cortex and in the brains of TgCRND8 mice, the later at multiple ages.Priming TgCRND8 mice with Il10 increases Aβ loads and blocks efficacy of subsequent mAb5 passive immunotherapy, whereas priming with Il6 priming reduces Aβ loads by itself and subsequent Aβ immunotherapy shows only a slightly additive effect. Transcriptomic data shows that (i) there are significant increases in the mRNA levels of Il6 and Il10 receptors in the TgCRND8 mouse model and temporal cortex of humans with AD and (ii) there is a great deal of variance in individual mouse brain and the human temporal cortex of these interleukins and their receptors.The underlying immune activation state can markedly affect the efficacy of passive Aβ immunotherapy. These results have important implications for ongoing human AD immunotherapy trials, as they indicate that underlying immune activation states within the brain, which may be highly variable, may influence the ability for passive immunotherapy to alter Aβ deposition." @default.
• W3157473458 created "2021-05-10" @default.
• W3157473458 creator A5009025157 @default.
• W3157473458 creator A5009533777 @default.
• W3157473458 creator A5016324624 @default.
• W3157473458 creator A5022864748 @default.
• W3157473458 creator A5030150965 @default.
• W3157473458 creator A5034589050 @default.
• W3157473458 creator A5042303080 @default.
• W3157473458 creator A5050832166 @default.
• W3157473458 creator A5056721836 @default.
• W3157473458 creator A5057196521 @default.
• W3157473458 creator A5058073147 @default.
• W3157473458 creator A5058688886 @default.
• W3157473458 creator A5060341726 @default.
• W3157473458 creator A5063679812 @default.
• W3157473458 creator A5065172118 @default.
• W3157473458 creator A5080705428 @default.
• W3157473458 creator A5082320489 @default.
• W3157473458 creator A5085629786 @default.
• W3157473458 creator A5087990147 @default.
• W3157473458 date "2021-05-06" @default.
• W3157473458 modified "2023-10-15" @default.
• W3157473458 title "Modulating innate immune activation states impacts the efficacy of specific Aβ immunotherapy" @default.
• W3157473458 cites W10297594 @default.
• W3157473458 cites W1444784109 @default.
• W3157473458 cites W1515023627 @default.
• W3157473458 cites W1528113046 @default.
• W3157473458 cites W1927066019 @default.
• W3157473458 cites W1977896329 @default.
• W3157473458 cites W1978567629 @default.
• W3157473458 cites W1986611577 @default.
• W3157473458 cites W1989206786 @default.
• W3157473458 cites W1994397669 @default.
• W3157473458 cites W1998981667 @default.
• W3157473458 cites W1999516517 @default.
• W3157473458 cites W2009174342 @default.
• W3157473458 cites W2009390338 @default.
• W3157473458 cites W2012815395 @default.
• W3157473458 cites W2024917017 @default.
• W3157473458 cites W2030260517 @default.
• W3157473458 cites W2033354781 @default.
• W3157473458 cites W2045311514 @default.
• W3157473458 cites W2058614488 @default.
• W3157473458 cites W2060851420 @default.
• W3157473458 cites W2067998641 @default.
• W3157473458 cites W2068777250 @default.
• W3157473458 cites W2082429191 @default.
• W3157473458 cites W2091723502 @default.
• W3157473458 cites W2096401612 @default.
• W3157473458 cites W2097867538 @default.
• W3157473458 cites W2098456470 @default.
• W3157473458 cites W2107804537 @default.
• W3157473458 cites W2116456562 @default.
• W3157473458 cites W2123047934 @default.
• W3157473458 cites W2133595485 @default.
• W3157473458 cites W2135780456 @default.
• W3157473458 cites W2136068368 @default.
• W3157473458 cites W2138274802 @default.
• W3157473458 cites W2138600972 @default.
• W3157473458 cites W2150231759 @default.
• W3157473458 cites W2155344647 @default.
• W3157473458 cites W2165907044 @default.
• W3157473458 cites W2167311426 @default.
• W3157473458 cites W2179438025 @default.
• W3157473458 cites W2190370706 @default.
• W3157473458 cites W2330649365 @default.
• W3157473458 cites W2346195607 @default.
• W3157473458 cites W2385703614 @default.
• W3157473458 cites W2466890096 @default.
• W3157473458 cites W2473453806 @default.
• W3157473458 cites W2510806376 @default.
• W3157473458 cites W2562304723 @default.
• W3157473458 cites W2617072792 @default.
• W3157473458 cites W2745518706 @default.
• W3157473458 cites W2753781001 @default.
• W3157473458 cites W2754683485 @default.
• W3157473458 cites W2767363231 @default.
• W3157473458 cites W2769095960 @default.
• W3157473458 cites W2777733505 @default.
• W3157473458 cites W2782007611 @default.
• W3157473458 cites W2784892576 @default.
• W3157473458 cites W2787612390 @default.
• W3157473458 cites W2809215238 @default.
• W3157473458 cites W2903601366 @default.
• W3157473458 cites W2923523140 @default.
• W3157473458 cites W2941510527 @default.
• W3157473458 cites W2946865729 @default.
• W3157473458 cites W2964503732 @default.
• W3157473458 cites W2969940182 @default.
• W3157473458 cites W2980270906 @default.
• W3157473458 cites W2992893037 @default.
• W3157473458 cites W2998795963 @default.
• W3157473458 cites W3014147424 @default.
• W3157473458 cites W3034168187 @default.
• W3157473458 cites W3034536401 @default.
• W3157473458 cites W3043048574 @default.
• W3157473458 cites W3097527510 @default.
• W3157473458 doi "https://doi.org/10.1186/s13024-021-00453-4" @default.
• W3157473458 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8103631" @default.

• next