Medicine and Health Sciences Commons^™

Methionine Sulfoxide Speciation In Mouse Hippocampus Revealed By Global Proteomics Exhibits Age- And Alzheimer’S Disease-Dependent Changes Targeted To Mitochondrial And Glycolytic Pathways, Filipa Blasco Tavares Pereira Lopes, Daniela Schlatzer, Mengzhen Li, Serhan Yılmaz, Rihua Wang, Xin Qi, Marzieh Ayati, Mehmet Koyutürk, Mark R. Chance

Computer Science Faculty Publications and Presentations

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with non-specific chemical oxidation from reactive oxygen species (ROS), whose chemistries are linked to various disease pathologies, including neurodegeneration. Emerging evidence shows MSox site occupancy is, in some cases, under enzymatic regulatory control, mediating cellular signaling, including phosphorylation and/or calcium signaling, and raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age-, sex-, and disease-dependent MSox speciation in the mouse hippocampus. …

Assessment Of Brain-Derived Extracellular Vesicle Enrichment For Blood Biomarker Analysis In Age-Related Neurodegenerative Diseases: An International Overview, Amanpreet Badhwar, Yael Hirschberg, Natalia Valle-Tamayo, Florencia Iulita, Chinedu Momoh, Anna Matton, Rawan Tarawneh, Robert Rissman, Aurélie Ledreux, Charisse Winston

Brain and Mind Institute

INTRODUCTION Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

METHODS NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases.

RESULTS A total of 82.1% of studies used polymer-based (ExoQuick) …

Assessment Of Brain-Derived Extracellular Vesicle Enrichment For Blood Biomarker Analysis In Age-Related Neurodegenerative Diseases: An International Overview, Amanpreet Badhwar, Yael Hirschberg, Natalia Valle-Tamayo, Florencia Iulita, Chinedu Momoh, Anna Matton, Rawan Tarawneh, Robert Rissman, Aurélie Ledreux, Charisse Winston

Brain and Mind Institute

INTRODUCTION Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

METHODS NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases.

RESULTS A total of 82.1% of studies used polymer-based (ExoQuick) …

Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays Sorghum Grain Polyphenolic Extracts Demonstrate Neuroprotective Effects Related To Alzheimer’S Disease In Cellular Assays, Nasim Rezaee, Eugene Hone, Hamid R. Sohrabi, Stuart Johnson, Leizhou Zhong, Prakhar Chatur, Stuart Gunzburg, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-β (Aβ) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer’s disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aβ- and tau-induced toxicity, …

The 2022 Symposium On Dementia And Brain Aging In Low- And Middle-Income Countries: Highlights On Research, Diagnosis, Care, And Impact, Raj Kalaria, Gladys Maestre, Simin Mahinrad, Daisy Acosta, Rufus Akinyemi, Suvarna Alladi, Ricardo Allegri, Faheem Arshad, Wambui Karanja, Chinedu Momoh

Brain and Mind Institute

Two of every three persons living with dementia reside in low- and middle-incomecountries (LMICs). The projected increase in global dementia rates is expected toaffect LMICs disproportionately. However, the majority of global dementia care costsoccur in high-income countries (HICs), with dementia research predominantly focus-ing on HICs. This imbalance necessitates LMIC-focused research to ensure thatcharacterization of dementia accurately reflects the involvement and specificities ofdiverse populations. Development of effective preventive, diagnostic, and therapeu-tic approaches for dementia in LMICs requires targeted, personalized, and harmonizedefforts. Our article represents timely discussions at the 2022 Symposium on Demen-tia and Brain Aging in LMICs that identified the foremost …

Role Of Neurocellular Endoplasmic Reticulum Stress Response In Alzheimer’S Disease And Related Dementias Risk, Miriam Aceves, Jose C. Granados, Ana C. Leandro, Juan M. Peralta, David C. Glahn, Sarah Williams-Blangero, Joanne E. Curran, John Blangero, Satish Kumar

School of Medicine Publications and Presentations

Currently, more than 55 million people around the world suffer from dementia, and Alzheimer’s Disease and Related Dementias (ADRD) accounts for nearly 60–70% of all those cases. The spread of Alzheimer’s Disease (AD) pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of ADRD’s causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study …

Mapping Of Alzheimer’S Disease Related Data Elements And The Nih Common Data Elements, Xubing Hao, Rashmie Abeysinghe, Fengbo Zheng, Paul E Schulz, The Alzheimer’S Disease Neuroimaging Initiative, Licong Cui

Student and Faculty Publications

Background

Alzheimer’s Disease (AD) is a devastating disease that destroys memory and other cognitive functions. There has been an increasing research effort to prevent and treat AD. In the US, two major data sharing resources for AD research are the National Alzheimer’s Coordinating Center (NACC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI); Additionally, the National Institutes of Health (NIH) Common Data Elements (CDE) Repository has been developed to facilitate data sharing and improve the interoperability among data sets in various disease research areas.

Method

To better understand how AD-related data elements in these resources are interoperable with each other, we …

Association Of Multiple Metabolic And Cardiovascular Markers With The Risk Of Cognitive Decline And Mortality In Adults With Alzheimer’S Disease And Ad-Related Dementia Or Cognitive Decline: A Prospective Cohort Study, Longjian Liu, Edward Gracely, Xiaopeng Zhao, Gediminas Gliebus, Nathalie May, Stella Volpe, Jingyi Shi, Rose Ann Dimaria-Ghalili, Howard Eisen

Division of Cardiology Faculty Papers

BACKGROUND AND OBJECTIVES: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD.

METHODS: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

A Novel Spatiotemporal Graph Convolutional Network Framework For Functional Connectivity Biomarkers Identification Of Alzheimer’S Disease, Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li

Student and Faculty Publications

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD.

METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Non-Coding Rnas Involved In The Molecular Pathology Of Alzheimer’S Disease: A Systematic Review, Reynand Jay Canoy, Jenica Clarisse Sy, Christian Deo Deguit, Caitlin Bridgette Castro, Lyoneil James Dimaapi, Beatrice Gabrielle Panlaqui, Wenzel Perian, Justine Yu, John Mark Velasco, Jesus Emmanuel Sevilleja, Anna Gibson

Ateneo School of Medicine and Public Health Publications

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass …

Cross-Sectional And Longitudinal Associations Between Treatment For Herpes Virus Infection And The Dispensing Of Antidementia Medicines: An Analysis Of The Australian Pharmaceutical Benefits Scheme Database, Stephanie Tan, Erin Kelty, Amy Page, Christopher Etherton-Beer, Frank Sanfilippo, Osvaldo P. Almeida

IHR Papers and Journal Articles

Background: Evidence from previous observational studies suggest that infection by herpes simplex virus (HSV) and varicella zoster virus (VZV) increase the risk of dementia.

Objective :To investigate if older adults exposed to HSV treatment have lower risk of dementia than the rest of the population.

Methods: We used the 10% Australian Pharmaceutical Benefits Scheme (PBS) database from 2013 to 2022 to ascertain the cross-sectional, time-series and longitudinal association between exposure to HSV treatment and the dispensing of antidementia medicines. Participants were men and women aged 60 years or older. We used Anatomical Therapeutic Chemical (ATC) codes to identify medicines dispensed …

The Impact Of Exercise On Blood-Based Biomarkers Of Alzheimer’S Disease In Cognitively Unimpaired Older Adults, Kelsey R. Sewell, Stephanie R. Rainey-Smith, Steve Pedrini, Jeremiah J. Peiffer, Hamid R. Sohrabi, Kevin Taddei, Shaun J. Markovic, Ralph N. Martins, Belinda M. Brown

Research outputs 2022 to 2026

Physical activity is a promising preventative strategy for Alzheimer’s disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer’s disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (A 42, A 40, A 42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and …

A Systematic Review Of Dementia Research Priorities, Manonita Ghosh, Pelden Chejor, Melanie Baker, Davina Porock

Research outputs 2022 to 2026

Introduction: Patient involvement is a critical component of dementia research priority-setting exercises to ensure that research benefits are relevant and acceptable to those who need the most. This systematic review synthesises research priorities and preferences identified by people living with dementia and their caregivers. Methods: Guided by Joanna Briggs Institute methodology, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, we conducted a systematic search in five electronic databases: CINAHL, Medline, PsycINFO, Web of Science and Scopus. The reference lists of the included studies were also manually searched. We combined quantitative and qualitative data for synthesis and descriptive thematic …

Alzheimer’S Disease Genetic Risk And Cognitive Reserve In Relationship To Long-Term Cognitive Trajectories Among Cognitively Normal Individuals, Corinne Pettigrew, Jurijs Nazarovs, Anja Soldan, Vikas Singh, Jiangxia Wang, Timothy Hohman, Logan Dumitrescu, Julia Libby, Brian Kunkle, Alden L. Gross, Sterling Johnson, Qiongshi Lu, Corinne Engelman, Colin L. Masters, Paul Maruff, Simon M. Laws, John C. Morris, Jason Hassenstab, Carlos Cruchaga, Susan M. Resnick, Melissa H. Kitner-Triolo, Yang An, Marilyn Albert

Research outputs 2022 to 2026

Background:

Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.

Methods:

Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by …

Large Multi-Ethnic Genetic Analyses Of Amyloid Imaging Identify New Genes For Alzheimer Disease, Muhammad Ali, Derek B. Archer, Priyanka Gorijala, Daniel Western, Jigyasha Timsina, Maria V. Fernández, Ting Chen Wang, Claudia L. Satizabal, Qiong Yang, Alexa S. Beiser, Ruiqi Wang, Gengsheng Chen, Brian Gordon, Tammie L.S. Benzinger, Chengjie Xiong, John C. Morris, Randall J. Bateman, Celeste M. Karch, Eric Mcdade, Alison Goate, Sudha Seshadri, Richard P. Mayeux, Reisa A. Sperling, Rachel F. Buckley, Keith A. Johnson, Hong-Hee Won, Sang-Hyuk Jung, Hang-Rai Kim, Sang W. Seo, Hee J. Kim, Elizabeth Mormino, Simon M. Laws, Kang-Hsien Fan, M. Ilyas Kamboh, Prashanthi Vemuri, Vijay K. Ramanan, Hyun-Sik Yang, Allen Wenzel, Hema S. R. Rajula, Aniket Mishra, Carole Dufouil, Stephanie Debette, Oscar L. Lopez, Steven T. Dekosky, Feifei Tao, Michael W. Nagle, Timothy J. Hohman, Yun J. Sung, Logan Dumitrescu, Carlos Cruchaga, Knight Alzheimer Disease Research Center (Knight Adrc), The Dominantly Inherited Alzheimer Network (Dian), Alzheimer's Disease Neuroimaging Initiative (Adni), Adni-Dod, A4 Study Team, The Australian Imaging Biomarkers, Lifestyle (Aibl) Study

Research outputs 2022 to 2026

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (AB) deposits in the brain and to study Alzheimer’s disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE 4; rs429358; = 0.35, SE = 0.01, P = 6.2 × 10–311, MAF = 0.19), driven by APOE 4, and five additional novel associations (APOE 2/rs7412; rs73052335/rs5117, rs1081105, …

How Does Apolipoprotein E Genotype Influence The Relationship Between Physical Activity And Alzheimer’S Disease Risk? A Novel Integrative Model, Jaisalmer De Frutos Lucas, Kelsey R. Sewell, Alejandra García-Colomo, Shaun Markovic, Kirk I. Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Background:

Wide evidence suggests that physical activity (PA) confers protection against Alzheimer’s disease (AD). On the other hand, the apolipoprotein E gene (APOE) ε₄ allele represents the greatest genetic risk factor for developing AD. Extensive research has been conducted to determine whether frequent PA can mitigate the increased AD risk associated with APOE ε₄. However, thus far, these attempts have produced inconclusive results. In this context, one possible explanation could be that the influence of the combined effect of PA and APOE ε₄ carriage might be dependent on the specific outcome measure utilised.

Main body:

In …

Postmortem Brain Imaging In Alzheimer's Disease And Related Dementias: The South Texas Alzheimer's Disease Research Center Repository, Karl Li, Tanweer Rashid, Jinqi Li, Nicolas Honnorat, Anoop Benet Nirmala, Elyas Fadaee, Di Wang, Sokratis Charisis, Gladys E. Maestre, Peter T. Fox

School of Medicine Publications and Presentations

Background:

Neuroimaging bears the promise of providing new biomarkers that could refine the diagnosis of dementia. Still, obtaining the pathology data required to validate the relationship between neuroimaging markers and neurological changes is challenging. Existing data repositories are focused on a single pathology, are too small, or do not precisely match neuroimaging and pathology findings.

Objective:

The new data repository introduced in this work, the South Texas Alzheimer’s Disease research center repository, was designed to address these limitations. Our repository covers a broad diversity of dementias, spans a wide age range, and was specifically designed to draw exact correspondences between …

Using Digital Assessment Technology To Detect Neuropsychological Problems In Primary Care Settings, David J Libon, Emily Frances Matusz, Stephanie Cosentino, Catherine C Price, Rod Swenson, Meagan Vermeulen, Terrie Beth Ginsberg, Adaora Obiageli Okoli-Umeweni, Leonard Powell, Robert Nagele, Sean Tobyne, Joyce Rios Gomes-Osman, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Screening for neurocognitive impairment and psychological distress in ambulatory primary and specialty care medical settings is an increasing necessity. The Core Cognitive Evaluation™ (CCE) is administered/scored using an iPad, requires approximately 8 min, assesses 3- word free recall and clock drawing to command and copy, asks questions about lifestyle and health, and queries for psychological distress. This information is linked with patients' self- reported concerns about memory and their cardiovascular risks.

METHODS: A total of 199 ambulatory patients were screened with the CCE as part of their routine medical care. The CCE provides several summary indices, and scores on …

The Alzheimer’S Disease Risk Factor Inpp5d Restricts Neuroprotective Microglial Responses In Amyloid Beta-Mediated Pathology, Joshua D Samuels, Katelyn A Moore, Hannah E Ennerfelt, Alexis M Johnson, Adeline E Walsh, Richard J Price, John R Lukens

Student and Faculty Publications

INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.

METHODS: We generated and investigated 5xFAD Inpp5d

RESULTS: SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d

DISCUSSION: …

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

Blood-Based Transcriptomic Biomarkers Are Predictive Of Neurodegeneration Rather Than Alzheimer's Disease, Artur Shvetcov, Shannon Thomson, Jessica Spathos, Ann-Na Cho, Heather M Wilkins, Shea J Andrews, Fabien Delerue, Timothy A Couttas, Jasmeen Kaur Issar, Finula Isik, Simranpreet Kaur, Eleanor Drummond, Carol Dobson-Stone, Shantel L Duffy, Natasha M Rogers, Daniel Catchpoole, Wendy A Gold, Russell H Swerdlow, David A Brown, Caitlin A Finney

Student and Faculty Publications

Alzheimer's disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as …

Sex-Dependent Effects Of Intestinal Microbiome Manipulation In A Mouse Model Of Alzheimer’S Disease, Harpreet Kaur, Suba Nookala, Surjeet Singh, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs

Biomedical Sciences Faculty Publications

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain …

An Ontology-Based Approach For Harmonization And Cross-Cohort Query Of Alzheimer’S Disease Data Resources, Xubing Hao, Xiaojin Li, Guo-Qiang Zhang, Cui Tao, Paul E Schulz, Licong Cui

Student and Faculty Publications

BACKGROUND: In the United States, the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) are two major data sharing resources for Alzheimer's Disease (AD) research. NACC and ADNI strive to make their data more FAIR (findable, interoperable, accessible and reusable) for the broader research community. However, there is limited work harmonizing and supporting cross-cohort interoperability of the two resources.

METHOD: In this paper, we leverage an ontology-based approach to harmonize data elements in the two resources and develop a web-based query system to search patient cohorts across the two resources. We first mapped data elements across …

A Novel Bioactive Peptide, T14, Selectively Activates Mtorc1 Signalling: Therapeutic Implications For Neurodegeneration And Other Rapamycin-Sensitive Applications, Sanskar Ranglani, Anna Ashton, Kashif Mahfooz, Joanna Komorowska, Alexandru Graur, Nadine Kabbani, Sara Garcia-Rates, Susan Greenfield

Student and Faculty Publications

T14 modulates calcium influx via the α-7 nicotinic acetylcholine receptor to regulate cell growth. Inappropriate triggering of this process has been implicated in Alzheimer's disease (AD) and cancer, whereas T14 blockade has proven therapeutic potential in in vitro, ex vivo and in vivo models of these pathologies. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth, however its hyperactivation is implicated in AD and cancer. T14 is a product of the longer 30mer-T30. Recent work shows that T30 drives neurite growth in the human SH-SY5Y cell line via the mTOR pathway. Here, we demonstrate that T30 induces an …

Predicting The Risk Of Alzheimer's Disease And Related Dementia In Patients With Mild Cognitive Impairment Using A Semi-Competing Risk Approach, Zhaoyi Chen, Yuchen Yang, Dazheng Zhang, Jingchuan Guo, Yi Guo, Xia Hu, Yong Chen, Jiang Bian

Student and Faculty Publications

Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) are a group of progressive neurodegenerative diseases. The progression of AD can be conceptualized as a continuum in which patients progress from normal cognition to preclinical AD (i.e., no symptoms but biological changes in the brain) to mild cognitive impairment (MCI) due to AD (i.e., mild symptoms but not interfere with daily activities), followed by increasing severity of dementia due to AD. Early detection and prediction models for the transition of MCI to AD/ADRD are needed, and efforts have been made to build predictions of MCI conversion to AD/ADRD. However, most existing studies …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Common Signaling Pathways Involved In Alzheimer's Disease And Stroke: Two Faces Of The Same Coin, Tushar Kanti Das, Bhanu Priya Ganesh, Kaneez Fatima-Shad

Student and Faculty Publications

Alzheimer's disease (AD) and stroke are two interrelated neurodegenerative disorders which are the leading cause of death and affect the neurons in the brain and central nervous system. Although amyloid-β aggregation, tau hyperphosphorylation, and inflammation are the hallmarks of AD, the exact cause and origin of AD are still undefined. Recent enormous fundamental discoveries suggest that the amyloid hypothesis of AD has not been proven and anti-amyloid therapies that remove amyloid deposition have not yet slowed cognitive decline. However, stroke, mainly ischemic stroke (IS), is caused by an interruption in the cerebral blood flow. Significant features of both disorders are …

Home-Based Tdcs For Apathy In Alzheimer’S Disease: A Protocol For A Randomized Double-Blinded Controlled Pilot Study, Antonio L Teixeira, Laís Bhering Martins, Thiago Macedo E Cordeiro, Lijin Jose, Robert Suchting, Holly M Holmes, Ron Acierno, Hyochol Ahn

Student and Faculty Publications

BACKGROUND: Apathy is among the most common behavioral symptoms in dementia and is consistently associated with negative outcomes in Alzheimer's disease (AD). Despite its prevalence and clinical relevance, available pharmacological and non-pharmacological strategies to treat apathy in AD have been marked, respectively, by potentially severe side effects and/or limited efficacy. Transcranial direct current stimulation (tDCS) is a relatively novel non-pharmacological method of neuromodulation with promising results. Compared to previous tDCS formats, recent technological advances have increased the portability of tDCS, which creates the potential for caregiver-administered, home use. Our study aims to evaluate the feasibility, safety, and efficacy of home-based …