Holden C. Williams
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View article: Kir6.2-K<sub>ATP</sub>channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis
Kir6.2-K<sub>ATP</sub>channels alter glycolytic flux to modulate cortical activity, arousal, and sleep-wake homeostasis Open
Summary Metabolism plays an important role in the maintenance of vigilance states (e.g. wake, NREM, and REM). Brain lactate fluctuations are a biomarker of sleep. Increased interstitial fluid (ISF) lactate levels are necessary for arousal …
View article: APOE genotype modifies microglial immunometabolism
APOE genotype modifies microglial immunometabolism Open
Background Metabolic dysfunction and neuroinflammation characterize Alzheimer’s disease (AD), but it is unclear if these two facets of the disease are linked. The E4 allele of Apolipoprotein E (APOE) is the strongest genetic risk factor fo…
View article: APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge Open
The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response: two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bul…
View article: <i>APOE4</i>drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes
<i>APOE4</i>drives transcriptional heterogeneity and maladaptive immunometabolic responses of astrocytes Open
Summary Apolipoprotein E4 (APOE4) is the strongest risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor of APOE while also being critical mediators of …
View article: <i>APOE</i> modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
<i>APOE</i> modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge Open
Summary The E4 allele of Apolipoprotein E ( APOE ) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we c…
View article: Exploring the Obesity Paradox in A Murine Model of Sepsis: Improved Survival Despite Increased Organ Injury in Obese Mice
Exploring the Obesity Paradox in A Murine Model of Sepsis: Improved Survival Despite Increased Organ Injury in Obese Mice Open
Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Res…
View article: Additional file 1 of APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis
Additional file 1 of APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis Open
Additional file 1. Differentially expressed genes in astrocytes (E4/E4 vs E3/E3).
View article: APOE4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis
APOE4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis Open
Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the E4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-ons…
View article: P4‐118: CEREBRAL METABOLISM AND ALZHEIMER'S DISEASE RISK: INVESTIGATING THE ROLE OF APOE USING STABLE‐ISOTOPE RESOLVED METABOLOMICS
P4‐118: CEREBRAL METABOLISM AND ALZHEIMER'S DISEASE RISK: INVESTIGATING THE ROLE OF APOE USING STABLE‐ISOTOPE RESOLVED METABOLOMICS Open
Apolipoprotein E (APOE) gene encodes for three different isoforms present in humans (E2, E3, and E4). Homozygous E4 individuals face up to a 15-fold increase risk for developing late-onset Alzheimer's Disease (AD). A hallmark of AD is a re…
View article: APOE and Alzheimer’s Disease: Neuroimaging of Metabolic and Cerebrovascular Dysfunction
APOE and Alzheimer’s Disease: Neuroimaging of Metabolic and Cerebrovascular Dysfunction Open
Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer's Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to …