Medicine and Health Sciences Commons^™

Infectious Hypothesis Of Alzheimer Disease, Charles E. Seaks, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Evaluation Of Aging And Genetic Mutation Variants On Tauopathy, Amber M. Tetlow

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is characterized by amyloid β plaques and neurofibrillary tau tangles (NFTs). While research has demonstrated amyloid pathology occurs prior to tau pathology, or tauopathy, tau has proven to be more toxic. Tauopathy is associated with cognitive declines and neurodegeneration. These findings have highlighted the importance of further understanding tauopathy. In the progression of tauopathy, there is an observable immune response that can be measured by glial cells such as microglia. Activated microglia are known to exacerbate tauopathy rather than reducing the pathology. Research has indicated that with increased age there is an increased risk for AD-related tauopathy …

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 …

Feasibility Of Dual-Task Gait To Estimate Alzheimer's Related Cognitive Decline In Down Syndrome, Kathryn L. Van Pelt, Lisa Mason Koehl, Allison M. Caban-Holt, Amelia J. Anderson-Mooney, Elizabeth Head, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Introduction: The striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.

Methods: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).

Results: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. …

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 …

The Promotion Of Physical Activity For The Prevention Of Alzheimer's Disease In Adults With Down Syndrome: Rationale And Design For A 12 Month Randomized Trial., Lauren T. Ptomey, Amanda N. Szabo-Reed, Laura E. Martin, Matthew S. Mayo, Richard A. Washburn, Anna M. Gorczyca, Rebecca J. Lepping, Phill Lee, Daniel Forsha, Joseph R. Sherman, Jessica C. Danon, Joseph E. Donnelly

Manuscripts, Articles, Book Chapters and Other Papers

Nearly all individuals with Down Syndrome (DS) display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. The limited research evaluating strategies for increasing MVPA in adults …

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 …

Brain Injury And Dementia In Pakistan: Current Perspectives, Maheen M. Adamson, Sadia Shakil, Tajwar Sultana, Muhammad Abul Hasan, Fatima Mubarak, Ather Enam, Muhammad A. Parvaz, Adeel Razi

Department of Radiology

Alzheimer's disease (AD) is the most common form of dementia, accounting for 50-75% of all cases, with a greater proportion of individuals affected at older age range. A single moderate or severe traumatic brain injury (TBI) is associated with accelerated aging and increased risk for dementia. The fastest growth in the elderly population is taking place in China, Pakistan, and their south Asian neighbors. Current clinical assessments are based on data collected from Caucasian populations from wealthy backgrounds giving rise to a "diversity" crisis in brain research. Pakistan is a lower-middle income country (LMIC) with an estimated one million people …

State Variability In The Prevalence And Healthcare Utilization Of Assisted Living Residents With Dementia, Kali S. Thomas, Wenhan Zhang, Portia Y. Cornell, Lindsey Smith, Brian Kaskie, Paula C. Carder

Institute on Aging Publications

Objectives: Almost 1 million older and disabled adults who require long‐term care reside in assisted living (AL), approximately 40% of whom have a diagnosis of Alzheimer's disease and related dementias (ADRD). States vary in their regulations specific to dementia care that may influence the presence of residents with ADRD in AL and their outcomes. The objectives of this study were to describe the state variability in the prevalence of ADRD among Medicare beneficiaries residing in larger (25+ bed) ALs and their healthcare utilization.

Design: Retrospective observational national study.

Participants: National cohort of 293,336 Medicare fee‐for‐service enrollees residing in larger (25+ …

Will "Social Distancing" Lead To Future "Research Distancing": A Reflection On Covid-19 Impacts On Alzheimer's Disease Research, Shoshana H. Bardach, Allison K. Gibson, Elizabeth K. Rhodus, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Coronavirus disease 19 (COVID-19) has dramatically altered everyday life, including the field of Alzheimer's disease (AD) research. This perspective article explores some of the ways in which COVID-19 has already impacted the field, anticipates some of the long-lasting effects, and explores strategies for addressing current and future needs. Areas of impact include study integrity, regulatory and industry issues, and participant engagement. Proposed strategies for addressing these challenges include analytic methods to deal with large degrees of missing data and development of patient-centered, user-friendly, remote data collection tools and assessments. We also highlight the importance of maintaining participant well-being as a …

Significance Of Blood And Cerebrospinal Fluid Biomarkers For Alzheimer's Disease: Sensitivity, Specificity And Potential For Clinical Use, C. D'Abramo, L. D'Adamio, L. Giliberto

Journal Articles

No abstract provided.

Efficacy Of Cpap Compared To Standard Pharmacotherapy In Reducing Cognitive Impairment Symptoms In Patients With Alzheimer's Disease, Nicholas Moylan

Capstone Showcase

This review analyzed the following question: In adults age 65 years old or older diagnosed with Alzheimer’s Disease (P), is nightly use of CPAP (I) more effective in reducing cognitive impairment symptoms (O) than standard pharmacotherapy options (C)? A literature search conducted through Google Scholar and PubMed granted six relevant articles that provided data for this review. No current studies compared CPAP treatment with pharmacotherapy, and each study used unique measures of cognitive function, making direct comparison of the two therapies difficult. Results demonstrated that first line pharmacotherapy can improve cognitive function, but only in limited way and only in …