Amyotroph Lateral Scler Frontotemporal Degener
November 2024
Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [F]fluorodeoxyglucose positron emission tomography ([F]FDG-PET) findings.
View Article and Find Full Text PDFAlterations in cholesterol metabolism in the brain have a major role in the physiology of Alzheimer's disease (AD). Oxysterols are cholesterol metabolites with multiple implications in memory functions and in neurodegeneration. Previous studies have shown detrimental effects of cholesterol metabolites in neurons, but its effect in glial cells is unknown.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the major form of dementia and a growing epidemic for which no disease-modifying treatments exist. AD is characterized by the early loss of synapses in the brain and, at later stages, neuronal death accompanied with progressive loss of cognitive functions. Here we focus on the mechanisms involved in the maintenance of the synapse and how their perturbation leads to synaptic loss.
View Article and Find Full Text PDFBackground: Many studies have indicated a relationship between diabetes and Alzheimer's disease (AD). However, the molecular mechanism underlying this association has not been clarified. Among several factors, insulin degrading enzyme (IDE), which plays roles in the degradation of both insulin and amyloid β (Aβ), has gained interest as a potential target in efforts to solve this puzzle.
View Article and Find Full Text PDFHypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced F-fluorodeoxyglucose uptake.
View Article and Find Full Text PDFSeveral studies demonstrated that Diabetes mellitus (DM) enhances the risk for Alzheimer's disease (AD). Although hyperglycemia and perturbed function of insulin signaling have been proposed to contribute to AD pathogenesis, the molecular mechanisms behind this association is not clear yet. Seladin-1 is an enzyme catalyzing the last step in cholesterol biosynthesis converting desmosterol to cholesterol.
View Article and Find Full Text PDFInflammation plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Although chronic inflammation in later stages of AD is well described, little is known about the inflammatory processes in preclinical or early stages of the disease prior to plaque deposition. In this study, we report that the inflammatory mediator S100A8 is increased with aging in the mouse brain.
View Article and Find Full Text PDFWe previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory in the Morris water maze test as compared to the wild type mice.
View Article and Find Full Text PDFBackground: Disturbances in cholesterol metabolism have been associated with hypertension and Alzheimer's disease (AD). We recently reported increased angiotensin-converting enzyme (ACE) activity and angiotensinogen (AGT) levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and AD. ACE activity positively correlated with plasma and CSF 27-hydroxycholesterol (27-OH) levels, an oxysterol that passes to the brain from the blood.
View Article and Find Full Text PDFDisturbances in cholesterol metabolism have been associated with hypertension and neurodegenerative disorders. Because cholesterol metabolism in the brain is efficiently separated from plasma cholesterol by the blood-brain barrier (BBB), it is an unsolved paradox how high blood cholesterol can cause an effect in the brain. Here, we discuss the possibility that cholesterol metabolites permeable to the BBB might account for these effects.
View Article and Find Full Text PDFAlzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide. AD has a multifactorial origin, resulting from an interaction between genetic susceptibility and environmental risk factors. Genetic, epidemiological, experimental and clinical data strongly suggest that the metabolism of cholesterol has an important role in AD pathogenesis.
View Article and Find Full Text PDFIn spite of the fact that cholesterol does not pass the blood-brain barrier, hypercholesterolemia has been linked to increase Alzheimer's disease (AD) risk. Hypertension is another risk factor and angiotensin converting enzyme (ACE) activity is known to be increased in AD. Furthermore, a lower incidence of AD has been reported in patients taking anti-hypertensive drugs.
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