Sex Dimorphism Profile of Alzheimer’s Disease-Type Pathologies in an APP/PS1 Mouse Model

Jiao, Shu‐Sheng; Bu, Xian‐Le; Liu, Yuhui; Zhu, Chi; Wang, Qinghua; Shen, Lin‐Lin; Liu, Chenghui; Wang, Ye‐Ran; Yao, Xiu-Qing; Wang, Yanjiang

doi:10.1007/s12640-015-9589-x

Cited by 91 publications

(75 citation statements)

References 43 publications

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“…Consistent with previous studies, males accumulated Aβ peptides and generated amyloid plaques more slowly than the females [63–65]. Perinatally choline-supplemented males exhibited dramatic resistance to Aβ buildup measured by ELISA and Western blot assays.…”

Section: Discussionsupporting

confidence: 90%

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice

et al. 2017

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Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites–specifically elevated amounts of β-C-terminal fragment (β-CTF) and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

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Section: Discussionsupporting

confidence: 90%

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice

et al. 2017

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“…However, increasing evidence implicated amyloid as a potential modulator in this sex difference. In transgenic mouse models of AD, female mice exhibited higher amyloid deposits in the brain [37-39], elevated beta-secretase activity and lower levels of neprilysin [39], indicating both up-regulated production and down-regulated clearance of amyloid in females. However, in human study, the results were mixed and inconclusive [6, 40].…”

Section: Discussionmentioning

confidence: 99%

Gender differences of neuropsychological profiles in cognitively normal older people without amyloid pathology

Zhang

Zhou

Wang

et al. 2017

Comprehensive Psychiatry

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Objective To investigate the impact of sex on cognition among cognitively normal older people without amyloid pathology. Methods The study sample consisted of 83 males (mean age 74 years, ranging from 65 to 88 years) and 111 females (mean age 72 years, ranging from 65 to 89 years) who were cognitively normal without amyloid pathology confirmed by Pittsburgh compound B PET scan. We examined the sex discrepancies in cognition using a comprehensive neuropsychological battery. Results Our data showed significantly greater advantage for women than men on the tasks of verbal memory and category fluency while better performance of naming in men than women when age, education and depressive symptoms were considered. Conclusion These findings highlight the importance of considering sex differences in the interpretation of cognitive data which contribute to clinical diagnosis of neurodegenerative disorders, such as Alzheimer's disease.

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“…This animal model was chosen according to previous studies reporting that female mice develop higher progressive memory impairment and AD-like neuropathology compared to male mice [20]. These transgenic mice express a Swedish (K594M/N595L) mutation of a chimeric mouse/human APP (mo/huAPP695swe), together with the human exon-9-deleted variant of PS1 (PS1-dE9).…”

Section: Methodsmentioning

confidence: 99%

Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways

et al. 2017

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The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.

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Sex Dimorphism Profile of Alzheimer’s Disease-Type Pathologies in an APP/PS1 Mouse Model

Cited by 91 publications

References 43 publications

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice

Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice

Gender differences of neuropsychological profiles in cognitively normal older people without amyloid pathology

Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways

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