M Paul Murphy’s research while affiliated with University of Kentucky and other places

... Increasing Aβ pathology is thought to further disrupt sleep by causing sleep fragmentation, reducing NREM sleep while increasing wakefulness 4,9,18,37,38 . Since disruptions of sleep and sleep-dependent brain rhythms actively contribute to Alzheimer's progression, enhancing NREM sleep and SWA might slow AD progression 17,29,39,40 . Indeed, optogenetic stimulation of neurons and astrocytes that increased SWA slowed pathophysiology associated with AD and rescued memory impairments in APP mice 17,29 . ...

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Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer’s disease mouse model

... Second, we observed similar findings in sensitivity analyses stratifying the group of women into younger vs. older women. However, in light of the important impact of menopause-related hormonal changes on sleep and the onset of sleep disorders [68] as well as on AD pathology [21], the subsample of women should ideally be stratified according to menopause status and use of hormone replacement therapy. Third, previous PET studies highlighted a female vulnerability to the accumulation of tau pathology particularly when considered in interaction with Aβ burden or APOE status [21,69], whereas we observed that males displayed higher plasma p-tau 181 levels in the present cohort. ...

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Sex differences in the relationships between 24-h rest-activity patterns and plasma markers of Alzheimer’s disease pathology

... Without entering into the discussion about whether aggregates are a cause or consequence of the diseases [55,56], the main challenge associated with targeting these proteins comes from the inherent biochemical properties of aggregation-prone proteins. ...

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The Potential of Metabolomics to Find Proper Biomarkers for Addressing the Neuroprotective Efficacy of Drugs Aimed at Delaying Parkinson’s and Alzheimer’s Disease Progression

... In general, high-cholesterol, high-glycemic, and high-sugar diets seem to be associated with higher AD risk (Moreira, 2013;Sparks, 2008), while low-glycemic diets high in omega-3 fatty acids such as the Mediterranean diet have been associated with decreased cognitive decline (Samadi et al., 2019). The high percentage of lipids in the brain makes it susceptible to fluctuations in dietary lipids, which can eventually affect the brain lipid profile and subsequent cognitive function (Amtul et al., 2013). However, this process is likely to be selective, as only certain compounds can enter the brain from the blood through the blood-brain barrier. ...

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Fatty acids and beyond: Age and Alzheimer's disease related changes in lipids reveal the neuro-nutraceutical potential of lipids in cognition

... Dogs feature effective models of a number of human diseases [101]. These include conditions affecting urinary [102], respiratory [103] and cardiovascular systems [104]. ...

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IN BETWEEN - Proteomics of dog biological fluids.

... Vascular endothelium just like neuronal and glial cells is capable of synthesizing, storing, and releasing reactive oxygen species (ROS) and immune molecules (IL-6, IL-1, chemokine (CC motif) ligand 2) in addition to vascular active substances upon in vitro interaction with A peptides and in human AD brains (Vukic et al., 2009). For instance, an excess of free superoxide radicals produced by endothelial cells upon A exposure can cause lipid peroxidation (Amtul et al., 2013; Oksman et al., 2006 ) by producing the oxidizing agents and scavenging the endothelium-derived relaxing factor (Thomas et al., 1996 ). Furthermore, the upregulation of a potent vasoconstrictor; endothelin 1 upon A binding to pleiotropic receptors for advanced glycation end products (RAGE) expressed by vascular endothelium, may also participate in regulating vascular inflammation in AD patients (Palmer et al., 2012). ...

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Why therapies for Alzheimer's disease do not work: Do we have consensus over the path to follow?

... TBI can lead to the disruption of the BBB (Habgood et al. 2007). The injury-induced rupture of cerebral blood vessels can allow blood contents to leak directly into the brain, contributing to secondary injury processes, including changes in cerebral blood flow, brain swelling, increased intracranial pressure, hypoxia/ischemia, inflammation, oxidative stress, and neuronal death (Habgood et al. 2007;Pop et al. 2013;Cash and Theus 2020). ...

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The canine blood-brain barrier in health and disease: focus on brain protection

... For instance, lower cerebral 17β-estradiol levels were observed in women with AD aged 80 years or older compared to healthy controls [149]. Progesterone, similarly to estrogens, plays a neuroprotective role through gamma-secretase [150] and the insulin-degrading enzyme (IDE) involved in the metabolism of Aβ [151]. Age-related reduction in progesterone levels in women correlates with the risk of AD [152]. ...

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Gut–Brain Axis: Focus on Sex Differences in Neuroinflammation

... The combination of existing and/or emerging therapeutics with PIP has become popular practice. With such intentions, Head et al. [45] tested a medical cocktail containing PIP (epigallocatechingallate 36.3% by wt., PIP 3.0% by wt., N-acetyl-l-cysteine 15.3% by wt., curcumin 36.3% by wt., and R-lipoic acid 9.1% by wt.) in aged dogs in an AD model. After 3 months of treatment, the dogs showed improved spatial attention and reduced cognitive impairment compared with non-treated age matching dogs, though brain and CSF Aβ remains unchanged. ...

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Piperine and Its Metabolite’s Pharmacology in Neurodegenerative and Neurological Diseases

... Unlike the regions heavily affected by Aβ plaque or neurofibrillary tangles, the SCN does not show significant pathology. Transgenic mouse models of AD expressing mutant human APP, tau, or both also exhibit circadian abnormalities, but establishing a direct link with pathology has proven challenging, hindering mechanistic understanding [117][118][119] . The Aβ peptide has been proposed to contribute to circadian dysfunction by promoting the degeneration of BMAL1 in cultured cells [120,121] . ...

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Circadian rhythm in neurodegenerative disease: the role of RNA modifications and potential application of RNA-based therapeutics