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Full-Text Articles in Medicine and Health Sciences

Ceramide Analog [18F]F-Hpa-12 Detects Sphingolipid Disbalance In The Brain Of Alzheimer’S Disease Transgenic Mice By Functioning As A Metabolic Probe, Simone M. Crivelli, Daan Van Kruining, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Andreas Paulus, Matthias Bauwens, Dusan Berkes, Helga E. De Vries, Monique T. Mulder, Jochen Walter, Etienne Waelkens, Rita Derua, Johannes V. Swinnen, Jonas Dehairs, Felix M. Mottaghy, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez Nov 2020

Ceramide Analog [18F]F-Hpa-12 Detects Sphingolipid Disbalance In The Brain Of Alzheimer’S Disease Transgenic Mice By Functioning As A Metabolic Probe, Simone M. Crivelli, Daan Van Kruining, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Andreas Paulus, Matthias Bauwens, Dusan Berkes, Helga E. De Vries, Monique T. Mulder, Jochen Walter, Etienne Waelkens, Rita Derua, Johannes V. Swinnen, Jonas Dehairs, Felix M. Mottaghy, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

The metabolism of ceramides is deregulated in the brain of Alzheimer’s disease (AD) patients and is associated with apolipoprotein (APO) APOE4 and amyloid-β pathology. However, how the ceramide metabolism changes over time in AD, in vivo, remains unknown. Distribution and metabolism of [18F]F-HPA-12, a radio-fluorinated version of the ceramide analog N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, was investigated in the brain of AD transgenic mouse models (FAD) on an APOE4 or APOE3 genetic background, by positron emission tomography and by gamma counter. We found that FAD mice displayed a higher uptake of [18F]F-HPA-12 in the brain, independently from the APOE4 …


Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes Dec 2017

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations & Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …


Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris Apr 2017

Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris

Electronic Thesis and Dissertation Repository

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …


Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy Jan 2015

Gene Expression And Alzheimer's Disease: Evaluation Of Gene Expression Patterns In Brain And Blood For An Alzheimer's Disease Mouse Model, Amanda Hazy

Senior Honors Theses

Previous studies have established a causative role for altered gene expression in development of Alzheimer’s disease (AD). These changes can be affected by methylation and miRNA regulation. In this study, expression of miRNA known to change methylation status in AD was assessed by qPCR. Genome-wide expression changes were determined by RNA-sequencing of mRNA from hippocampus and blood of control and AD mice. The qPCR data showed significantly increased expression of Mir 17 in AD, and sequencing data revealed 230 genes in hippocampus, 58 genes in blood, and 8 overlapping genes showing significant differential expression (p value ≤ 0.05). Expression data …