Medicine and Health Sciences Commons^™

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) …

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

Journal Articles

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 …

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 …

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 Faculty Scholarship

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 …

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 …

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

Journal Articles

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

Journal Articles

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 …

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 …

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …

Relationship Between Cognitive Performance, Physical Activity, And Socio-Demographic/Individual Characteristics Among Aging Americans, Imtiaz Masfique Dowllah, Juan Carlos Lopez-Alvarenga, Gladys Maestre, Ulku S. Karabulut, Michael Lehker, Murat Karabulut

School of Medicine Publications and Presentations

Background: Physical activity (PA) has emerged as a promising approach to delay Alzheimer’s disease and related dementias, but the optimal intensity of PA to improve cognitive health remains unknown.

Objective: To evaluate the association between duration and intensity of PA and cognitive domains (executive function, processing speed, and memory) in aging Americans.

Methods: Linear regressions in hierarchical blocks for variable adjustment and the size of effect (η2) were analyzed by using the data of 2,377 adults (age = 69.3±6.7 years) from the NHANES 2011–2014.

Results: Participants with 3–6 h/week of vigorous- and > 1 h/week of moderate-intensity PA scored significantly higher …

Pharm In Action: New Hopes For Alzheimer’S Treatment, Basil Considine

URGENT Matters

No abstract provided.

Early Visual Alterations In Individuals At-Risk Of Alzheimer’S Disease: A Multidisciplinary Approach, Inés López-Cuenca, Alberto Nebreda, Alejandra García-Colomo, Elena Salobrar-García, Jaisalmer De Frutos-Lucas, Ricardo Bruña, Ana I. Ramírez, Federico Ramirez-Toraño, Juan J. Salazar, Ana Barabash, Pedro Gil, Fernando Maestú, José M. Ramírez, Rosa De Hoz

Research outputs 2022 to 2026

Background: The earliest pathological features of Alzheimer’s disease (AD) appear decades before the clinical symptoms. The pathology affects the brain and the eye, leading to retinal structural changes and functional visual alterations. Healthy individuals at high risk of developing AD present alterations in these ophthalmological measures, as well as in resting-state electrophysiological activity. However, it is unknown whether the ophthalmological alterations are related to the visual-related electrophysiological activity. Elucidating this relationship is paramount to understand the mechanisms underlying the early deterioration of the system and an important step in assessing the suitability of these measures as early biomarkers of disease. …

Estimating Dementia Risk In An African American Population Using The Dctclock, Marissa Ciesla, Jeff Pobst, Joyce Gomes-Osman, Melissa Lamar, Lisa L Barnes, Russell Banks, Ali Jannati, David Libon, Rodney Swenson, Sean Tobyne, David Bates, John Showalter, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research …

Efficient Training On Alzheimer’S Disease Diagnosis With Learnable Weighted Pooling For 3d Pet Brain Image Classification, Xin Xing, Muhammad Usman Rafique, Gongbo Liang, Hunter Blanton, Zu Zhang, Chris Wang, Nathan Jacobs, Ai-Ling Lin

Computer Science Faculty Publications

Three-dimensional convolutional neural networks (3D CNNs) have been widely applied to analyze Alzheimer’s disease (AD) brain images for a better understanding of the disease progress or predicting the conversion from cognitively impaired (CU) or mild cognitive impairment status. It is well-known that training 3D-CNN is computationally expensive and with the potential of overfitting due to the small sample size available in the medical imaging field. Here we proposed a novel 3D-2D approach by converting a 3D brain image to a 2D fused image using a Learnable Weighted Pooling (LWP) method to improve efficient training and maintain comparable model performance. By …

Traumatic Brain Injury-Associated Epigenetic Changes And The Risk For Neurodegenerative Diseases, Paul Smolen, Pramod K Dash, John B Redell

Journal Articles

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer's or Parkinson's are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute …

Traumatic Brain Injury-Associated Epigenetic Changes And The Risk For Neurodegenerative Diseases, Paul Smolen, Pramod K Dash, John B Redell

Journal Articles

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer's or Parkinson's are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute …

Utility Of Dna Methylation As A Biomarker In Ageing And Alzheimer’S Disease, Lidija Milicic, Tenielle Porter, Michael Vacher, Simon M. Laws

Research outputs 2022 to 2026

Epigenetic mechanisms such as DNA methylation have been implicated in a number of diseases including cancer, heart disease, autoimmune disorders, and neurodegenerative diseases. While it is recognized that DNA methylation is tissue-specific, a limitation for many studies is the ability to sample the tissue of interest, which is why there is a need for a proxy tissue such as blood, that is reflective of the methylation state of the target tissue. In the last decade, DNA methylation has been utilized in the design of epigenetic clocks, which aim to predict an individual’s biological age based on an algorithmically defined set …

The Impact Of Routine Vaccinations On Alzheimer's Disease Risk In Persons 65 Years And Older: A Claims-Based Cohort Study Using Propensity Score Matching, Kristofer Harris, Yaobin Ling, Avram S Bukhbinder, Luyao Chen, Kamal N Phelps, Gabriela Cruz, Jenna Thomas, Yejin Kim, Xiaoqian Jiang, Paul E Schulz

Journal Articles

Background:

Accumulating evidence suggests that adult vaccinations can reduce the risk of developing Alzheimer’s disease (AD) and Alzheimer’s disease related dementias.

Objective:

To compare the risk for developing AD between adults with and without prior vaccination against tetanus and diphtheria, with or without pertussis (Tdap/Td); herpes zoster (HZ); or pneumococcus.

Methods:

A retrospective cohort study was performed using Optum’s de-identified Clinformatics® Data Mart Database. Included patients were free of dementia during a 2-year look-back period and were≥65 years old by the start of the 8-year follow-up period. We compared two similar cohorts identified using propensity score matching (PSM), one vaccinated …

G-Quadruplexes And Associated Proteins In Aging And Alzheimer’S Disease, M J Vijay Kumar, Rodrigo Morales, Andrey S Tsvetkov

Journal Articles

Aging is a prominent risk factor for many neurodegenerative disorders, such as Alzheimer's disease (AD). Alzheimer's disease is characterized by progressive cognitive decline, memory loss, and neuropsychiatric and behavioral symptoms, accounting for most of the reported dementia cases. This disease is now becoming a major challenge and burden on modern society, especially with the aging population. Over the last few decades, a significant understanding of the pathophysiology of AD has been gained by studying amyloid deposition, hyperphosphorylated tau, synaptic dysfunction, oxidative stress, calcium dysregulation, and neuroinflammation. This review focuses on the role of non-canonical secondary structures of DNA/RNA G-quadruplexes (G4s, …