Gender effect on the accumulation of hyperphosphorylated tau in the brain of locus-ceruleus-injured APP-transgenic mouse

Oikawa, Naoto; Ogino, Kōichi; Masumoto, Takumi; Yamaguchi, Hideyo; Yanagisawa, Katsuhiko

doi:10.1016/j.neulet.2009.11.005

Cited by 19 publications

(17 citation statements)

References 40 publications

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“…In addition, tau levels did not differ in intact males and females [115,123]. Similar variation in sex differences of Aβ levels, amyloid plaque deposition, and tau is observed in response to stress, pharmacologic, and genetic manipulations of mouse models of AD [114,128,131-134,136-139]. …”

Section: Review Of Studies On Sex Differences In Mouse Models Of Admentioning

confidence: 88%

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

2012

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Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases.

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Section: Review Of Studies On Sex Differences In Mouse Models Of Admentioning

confidence: 88%

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

2012

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“…More work is needed to clarify the effect of sex on AD pathology. In an animal model of AD, amyloid precursor protein-transgenic mouse, injury to locus ceruleus caused amyloid-related accumulation of phosphorylated tau in female, not male, rats [44]. Although pathogenetic basis of this sex difference was not investigated, difference in testosterone level was assumed to be responsible by affecting molecular pathways of stress induced taupathy [44].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in Alzheimer’s disease and common neuropathologies of aging

et al. 2018

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Alzheimer’s dementia is significantly more common in women than in men. However, few pathological studies have addressed sex difference in Alzheimer’s disease (AD) and other brain pathologies. We leveraged post mortem data from 1453 persons who participated in one of two longitudinal community-based studies of older adults, the Religious Orders Study and the Rush Memory and Aging Project. Postmortem examination identified AD pathologies, neocortical Lewy bodies, DNA-binding protein 43 (TDP-43), hippocampal sclerosis, gross and micro infarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy. Linear and logistic regressions examined the association of sex with each of the pathologic measures. Two thirds of subjects were women (n=971; 67%), with a mean age-at-death of 89.8 (SD=6.6) years in women and 87.3 (SD=6.6) in men. Adjusted for age and education, women had higher levels on a global measure of AD pathology (estimate=0.102, SE=0.022, p<0.001), and tau tangle density in particular (estimate=0.334, SE=0.074, p<0.001), and there was a borderline difference between women and men in amyloid-β load (estimate=0.124, SE=0.065, p=0.056). In addition, compared to men, women were more likely to have more severe arteriolosclerosis (OR=1.28, 95% CI:1.04–1.58, p=0.018), and less likely to have gross infarcts (OR=0.78, 95% CI:0.61–0.98, p=0.037), although the association with gross infarct was attenuated after controlling for vascular risk factors. These data help elucidate the neuropathologic footprint of sex difference in AD and other common brain pathologies of ageing.

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“…Treatment of AD transgenic mice with DSP-4, a neurotoxin which selectively ablates noradrenergic neurons, increases Aβ deposition (Heneka et al, 2006; Kalinin et al, 2007; Jardanhazi-Kurutz et al, 2010), impairs spatial memory (Jardanhazi-Kurutz et al, 2010) and alters α 1 , α 2 , and β 1 receptor binding sites and mRNA expression (Jardanhazi-Kurutz et al, 2011). DSP-4 treatment also increases the levels of accumulated hyperphosphorylated tau in cortices of female APP-SL mice (Oikawa et al, 2010). APP/PS1 mice crossed with DβH −/− mice, which are unable to synthesize norepinephrine, have compromised LTP and maze performance, which is worse than in either of the single mutants alone (APP/PS1 or DβH −/− ) (Hammerschmidt et al, 2013).…”

Section: Potential Involvement Of Noradrenergic Dysregulation In Ad Pmentioning

confidence: 99%

Noradrenergic dysfunction in Alzheimer's disease

et al. 2015

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The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

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Gender effect on the accumulation of hyperphosphorylated tau in the brain of locus-ceruleus-injured APP-transgenic mouse

Cited by 19 publications

References 40 publications

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

Sex differences in Alzheimer’s disease and common neuropathologies of aging

Noradrenergic dysfunction in Alzheimer's disease

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