Life Sciences Commons^™

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 …

Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.

Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.

Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Nutraceutical Potential For Alzheimer's Disease Treatment, Alex Gewecke

Undergraduate Research Journal

Alzheimer’s disease (AD) is a progressive disorder involving buildup of excessive amounts of proteins such as beta amyloid in the brain that leads to memory loss, inability to perform daily functions, and an early death. By 2060, the number of cases is forecast to nearly triple current numbers. Age is the primary risk factor for AD and no new drugs have been approved since 2003. Nutraceuticals, a broad category of substances that can be utilized for both medicinal and nutritional purposes may be able to help, which is why they are being more widely researched. Overall, a number of attempts …

Meta-Analysis Of The Alzheimer's Disease Human Brain Transcriptome And Functional Dissection In Mouse Models., Ying-Wooi Wan, Rami Al-Ouran, Carl G Mangleburg, Thanneer M Perumal, Tom V Lee, Katherine Allison, Vivek Swarup, Cory C Funk, Chris Gaiteri, Mariet Allen, Minghui Wang, Sarah M Neuner, Catherine C Kaczorowski, Vivek M Philip, Gareth R Howell, Heidi Martini-Stoica, Hui Zheng, Hongkang Mei, Xiaoyan Zhong, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson, Ping-Chieh Pao, Li-Huei Tsai, Jean-Vianney Haure-Mirande, Michelle E Ehrlich, Paramita Chakrabarty, Yona Levites, Xue Wang, Eric B Dammer, Gyan Srivastava, Sumit Mukherjee, Solveig K Sieberts, Larsson Omberg, Kristen D Dang, James A Eddy, Phil Snyder, Yooree Chae, Sandeep Amberkar, Wenbin Wei, Winston Hide, Christoph Preuss, Ayla Ergun, Phillip J Ebert, David C Airey, Sara Mostafavi, Lei Yu, Hans-Ulrich Klein, Accelerating Medicines Partnership, Alzheimer’S Disease Consortium, Gregory W Carter, David A Collier, Todd E Golde, Allan I Levey, David A Bennett, Karol Estrada, T Matthew Townsend, Bin Zhang, Eric Schadt, Philip L De Jager, Nathan D Price, Nilüfer Ertekin-Taner, Zhandong Liu, Joshua M Shulman, Lara M Mangravite, Benjamin A Logsdon

Articles, Abstracts, and Reports

We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic …

Investigation Of The Role Of Heparin-Binding Pocket In Amyloid Fibrils Formation Of Fgf-1, I Gusti Ayu Agung Septiari

Graduate Theses and Dissertations

Human acidic fibroblast growth factor (aFGF/hFGF-1) is one of the promising molecules to be investigated to generate an in-depth understanding of the pathological mechanism of Alzheimer's disease (AD) neurodegenerative disorder characterized by the presence of amyloid fibrils. Some in vivo and human brain tissue studies proved the correlation of high-level expression of FGF-1-induced neuroinflammation and the occurrence of AD. The presence of amyloid fibrils as a hallmark of AD can be related to the generic property of the proteins to form amyloid fibrils; High level of FGF-1, in this case, may contribute to the formation of amyloid fibrils. As a …

Elucidating The Effects Of Glucose Toxicity On Tauopathy And Aging, Lukas Fluitt

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Diabetes patients are at higher risk of contracting an age-related neurodegenerative disease such as Alzheimer’s disease (AD). However, the mechanisms which link these diseases are poorly understood. We hypothesize that glucose and elevated levels of the glycolysis by product advanced glycation end-products (AGEs), may be involved. AGEs accumulate with age and are elevated in both diabetic and AD patients. Diabetes is a metabolic disorder for which consumption of sugar-rich diets is a major risk factor and is central to etiology in the vast majority of cases.

We show that transgenic C. elegans expressing wild type (WT) human tau fed a …

Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song

Arts & Sciences Electronic Theses and Dissertations

Carriers of the R47H allele of the microglia-specific lipid receptor TREM2 have a greatly increased risk of developing Alzheimerճ disease. The objective of this dissertation is to develop further mechanistic knowledge about how TREM2 is regulated and how TREM2 mutations affect microglia and neurodegeneration. Using an in vitro reporter assay, we find that several AD risk-associated TREM2 mutations decrease ligand-dependent activation. Using humanized TREM2 mice, we find that in vivo, the R47H mutation leads to reduced microglia activation and response to A_, as well as decreased shedding of soluble TREM2. These results suggest that TREM2 is protective during disease. We …

A Study Of The Antioxidant Versus Pro-Oxidant Nature Of The Amyloid Beta Peptide And An Analysis Of The Natural Products, Isorhamnetin And Narignenin, As Antioxidants, Kaylee Holmes

Honors Theses

Alzheimer’s disease is a neurodegenerative disorder with no cure. Due to the widespread effects of this disease, abundant research efforts have gone towards finding a cure. The amyloid beta (Ab) peptide has been shown to be a potential cause of the disease due to destructive effects on tissues that it can have both by itself and through reactive oxygen species (ROS) generation. This study was performed in order to assess the structural properties of Ab₄₂monomers, fibrils and oligomers, to assess the antioxidant versus pro-oxidant behavior of the Ab peptide, and to assess the antioxidant nature of the natural …

Concordant Peripheral Lipidome Signatures In Two Large Clinical Studies Of Alzheimer’S Disease, Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle

Research outputs 2014 to 2021

© 2020, The Author(s). Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid …