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.

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 …

Higher Csf Strem2 Attenuates Apoe4-Related Risk For Cognitive Decline And Neurodegeneration, Nicolai Franzmeier, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, Leslie Shaw, John Q. Trojanowski, Martin Dichgans, Gernot Kleinberger, Christian Haass, Michael Ewers, Michael Weiner, Paul Aisen, Gerald Novak, Robert C. Green, Tom Montine, Ronald Petersen, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Laurel Beckett, Danielle Harvey, John Kornak, Clifford R. Jack, Anders Dale, Matthew Bernstein, Joel Felmlee

Medical Biophysics Publications

Background: The Apolipoprotein E ϵ4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. Methods: We included 708 subjects ranging from cognitively normal (CN, n = …

Risk Prediction Of Late-Onset Alzheimer’S Disease Implies An Oligogenic Architecture, Qian Zhang, Julia Sidorenko, Baptiste Couvy-Duchesne, Riccardo E. Marioni, Margaret J. Wright, Alison M. Goate, Edoardo Marcora, Kuan-Lin Huang, Tenielle Porter, Simon M. Laws, Perminder S. Sachdev, Karen A. Mather, Nicola J. Armstrong, Anbupalam Thalamuthu, Henry Brodaty, Loic Yengo, Jian Yeng, Naomi R. Wray Robertson, Allan F. Mcrae, Peter M. Visscher, Steven Collins, Christine Thai, Brett Trounson, Kate Lennon, Qiao Xin Li, Fernanda Yevenes Ugarte, Irene Volitakis, Michael Vovos, Australian Imaging Biomarkers And Lifestyle

Research outputs 2014 to 2021

© 2020, The Author(s). Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting …

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 …

Challenges Of Doing Alzheimer’S Research In Costa Rica And Some Possible Solutions, Felipe Mejias

English Language Institute

Alzheimer's disease is a public health priority which has been researched for many years in the hope of finding a cure soon. Costa Rica has made significant progress in many areas of research; however, the research carried out in the country on Alzheimer's disease is very scarce. The present poster presents the challenges of developing scientific Alzheimer’s research in Costa Rica by reviewing current scientific research on Alzheimer's in Costa Rica and by conducting interviews with Costa Rican professionals who have conducted Alzheimer's research. The lack of investigative training of doctors, the difficulties in accessing patient data, and the lack …

World-Wide Fingers Network: A Global Approach To Risk Reduction And Prevention Of Dementia, Miia Kivipelto, Francesca Mangialasche, Heather M. Snyder, Ricardo Allegri, Sandrine Andrieu, Hidenori Arai, Laura Baker, Sylvie Belleville, Henry Brodaty, Sonia M. Brucki, Ismael Calandri, Paulo Caramelli, Christopher Chen, Howard Chertkow, Effie Chew, Seong H. Choi, Neerja Chowdhary, Lucía Crivelli, Rafael De La Torre, Yifeng Du, Tarun Dua, Mark Espeland, Howard H. Feldman, Maris Hartmanis, Tobias Hartmann, Megan Heffernan, Christiani J. Henry, Chang H. Hong, Krister Hakansson, Takeshi Iwatsubo, Jee H. Jeong, Gustavo Jimenez-Maggiora, Edward H. Khoo, Lenore J. Launer, Jenni Lehtisalo, Francisco Lopera, Pablo Martinez-Lage, Ralph Martins, Lefkos Middleton, Jose L. Molinuevo, Manuel Montero-Odasso, So Y. Moon, Kristal Morales-Perez, Ricardo Nitrini, Haakon B. Nygaard, Yoo K. Park, Markku Peltonen, Chengxuan Qiu, Yakeel T. Quiroz, Rema Raman, Naren Rao, Vijayalakshmi Ravindranath, Anna Rosenberg, Takashi Sakurai, Rosa M. Salinas, Philip Scheltens, Gustavo Sevlever, Hilkka Soininen, Ana L. Sosa, Claudia K. Suemoto, Mikel Tainta-Cuezva, Lina Velilla, Yongxiang Wang, Rachel Whitmer, Xin Xu, Lisa J. Bain, Alina Solomon, Tiia Ngandu, Maria C. Carrillo

Research outputs 2014 to 2021

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk …

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 …

Systematic Review Protocol For Assessing Central Auditory Functions Of Alzheimer's Disease And Its Preclinical Stages, Dona M.P. Jayakody, Hadeel Y. Tarawneh, Holly K. Menegola, Jessica M. Yiannos, Peter L. Friedland, Wayne J. Wilson, Ralph N. Martins, Hamid R. Sohrabi

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction A number of studies have reported an association between peripheral hearing impairment, central auditory processing and Alzheimer's disease (AD) and its preclinical stages. Both peripheral hearing impairment and central auditory processing disorders are observed many years prior to the clinical manifestation of AD symptoms, hence, providing a long window of opportunity to investigate potential interventions against neurodegenerative processes. This paper outlines the protocol for a systematic review of studies examining the central auditory processing functions in AD and …

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+ …

Basal Forebrain Volume Reliably Predicts The Cortical Spread Of Alzheimer's Degeneration, Sara Fernández-Cabello, Martin Kronbichler, Koene R.A. Van Dijk, James A. Goodman, R. Nathan Spreng, Taylor W. Schmitz

Brain and Mind Institute Researchers' Publications

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. Alzheimer's disease neurodegeneration is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model used to guide in vivo human neuroimaging and non-human animal research assumes that Alzheimer's degeneration starts in the entorhinal cortices, before spreading to the temporoparietal cortex. Challenging this model, we previously provided evidence that in vivo markers of neurodegeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, …

Role Of Endolysosomes And Inter-Organellar Signaling In Brain Disease, Zahra Afghah, Xuesong Chen, Jonathan David Geiger

Biomedical Sciences Faculty Publications

Endosomes and lysosomes (endolysosomes) are membrane bounded organelles that play a key role in cell survival and cell death. These acidic intracellular organelles are the principal sites for intracellular hydrolytic activity required for the maintenance of cellular homeostasis. Endolysosomes are involved in the degradation of plasma membrane components, extracellular macromolecules as well as intracellular macromolecules and cellular fragments. Understanding the physiological significance and pathological relevance of endolysosomes is now complicated by relatively recent findings of physical and functional interactions between endolysosomes with other intracellular organelles including endoplasmic reticulum, mitochondria, plasma membranes, and peroxisomes. Indeed, evidence clearly indicates that endolysosome dysfunction …

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.

Evaluation Of 18F-Iam6067 As A Sigma-1 Receptor Pet Tracer For Neurodegeneration In Vivo In Rodents And In Human Tissue, François Xavier Lepelletier, Matthias Vandesquille, Marie Claude Asselin, Christian Prenant, Andrew C. Robinson, David M.A. Mann, Michael Green, Elizabeth Barnett, Samuel D. Banister, Marco Mottinelli, Christophe Mesangeau, Christopher R. Mccurdy, Inga B. Fricke, Andreas H. Jacobs, Michael Kassiou, Hervé Boutin

Faculty and Student Publications

© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. The sigma 1 receptor (S1R) is widely expressed in the CNS and is mainly located on the endoplasmic reticulum. The S1R is involved in the regulation of many neurotransmission systems and, indirectly, in neurodegenerative diseases. The S1R may therefore represent an interesting neuronal biomarker in neurodegenerative diseases such as Parkinson's (PD) or Alzheimer's diseases (AD). Here we present the characterisation of the S1R-specific 18F-labelled tracer 18F-IAM6067 in two animal models and in human …

Elecsys Csf Biomarker Immunoassays Demonstrate Concordance With Amyloid-Pet Imaging, James A. Doecke, Larry Ward, Samantha C. Burnham, Victor L. Villemagne, Qiao-Xin Li, Steven Collins, Christopher J. Fowler, Ekaterina Manuilova, Monika Widmann, Stephanie R. Rainey-Smith, Ralph N. Martins, Colin L. Masters, Aibl Research Group

Research outputs 2014 to 2021

Background: β-amyloid (Aβ) positron emission tomography (PET) imaging is currently the only Food and Drug Administration-approved method to support clinical diagnosis of Alzheimer's disease (AD). However, numerous research studies support the use of cerebrospinal fluid (CSF) biomarkers, as a cost-efficient, quick and equally valid method to define AD pathology. Methods: Using automated Elecsys® assays (Roche Diagnostics) for Aβ (1-42) (Aβ42), Aβ (1-40) (Aβ40), total tau (tTau) and phosphorylated tau (181P) (pTau), we examined CSF samples from 202 participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing cohort, to demonstrate the concordance with pathological AD via PET imaging. …

Amylin And Beta Amyloid Proteins Interact To Form Amorphous Heterocomplexes With Enhanced Toxicity In Neuronal Cells, Prashant Bharadwaj, Tanya Solomon, Bikash Sahoo, Katarzyna Ignasiak, Scott Gaskin, Joanne Rowles, Guiseppe Verdile, Mark Howard, Charles S. Bond, Ayyalusamy Ramamoorthy, Ralph Martins, Philip Newsholme

Research outputs 2014 to 2021

Human pancreatic islet amyloid polypeptide (hIAPP) and beta amyloid (Aβ) can accumulate in Type 2 diabetes (T2D) and Alzheimer’s disease (AD) brains and evidence suggests that interaction between the two amyloidogenic proteins can lead to the formation of heterocomplex aggregates. However, the structure and consequences of the formation of these complexes remains to be determined. The main objective of this study was to characterise the different types and morphology of Aβ-hIAPP heterocomplexes and determine if formation of such complexes exacerbate neurotoxicity. We demonstrate that hIAPP promotes Aβ oligomerization and formation of small oligomer and large aggregate heterocomplexes. Co-oligomerized Aβ42-hIAPP mixtures …

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 …