title: Multiple inflammatory pathways are involved in the development and progression of cognitive deficits in APPswe/PS1dE9 mice.
abstract: Increased accumulation of amyloid-beta peptide (Aβ) and neuroinflammation is known to exist within the Alzheimer's disease (AD) brain. However, it remains unclear which form of Aβ pathologies triggers neuroinflammation and whether increased neuroinflammation contributes to cognitive deficits in AD. In the present study we found that increased inflammatory responses might occur early in preplaque APPswe/PS1dE9 mice, and were significantly enhanced in both early- and late-plaque APPswe/PS1dE9 mice. Correlational analysis revealed that multiple inflammatory indexes significantly correlated with soluble Aβ level, rather than amyloid plaque burden or insoluble Aβ level, in APPswe/PS1dE9 mice. Moreover, multiple inflammatory indexes highly correlated with the impaired spatial learning and memory in APPswe/PS1dE9 mice. Collectively, these results provide evidence that inflammatory responses might be likely triggered by soluble toxic Aβ species. Importantly, we demonstrate for the first time that multiple inflammatory pathways might be involved in the development and progression of cognitive deficits in APPswe/PS1dE9 mice, suggesting that a pharmacological approach targeting multiple inflammatory pathways may be a novel promising strategy to prevent or delay AD.
authors.affiliation: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an City, Shaanxi Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Miao
authors.initials: M
authors.lastname: Bai
authors.forename: Ye
authors.initials: Y
authors.lastname: Xi
authors.forename: Jian
authors.initials: J
authors.lastname: Hao
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Changjun
authors.initials: C
authors.lastname: Su
authors.forename: Gesheng
authors.initials: G
authors.lastname: Lei
authors.forename: Jianting
authors.initials: J
authors.lastname: Miao
authors.forename: Zhuyi
authors.initials: Z
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics; D015398:Signal Transduction
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1