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Articles 1 - 30 of 40
Full-Text Articles in Medicine and Health Sciences
In Sickness And In Health-Type I Interferon And The Brain, Wei Cao
In Sickness And In Health-Type I Interferon And The Brain, Wei Cao
Journal Articles
Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …
Effects Of Music Therapy For Patients With Alzheimer's, Anastasiya Kapatsyna, Evelyn Staples, Meleah Sparks, Paige Schubert
Effects Of Music Therapy For Patients With Alzheimer's, Anastasiya Kapatsyna, Evelyn Staples, Meleah Sparks, Paige Schubert
NURS 320: Evidence-Based Nursing Student Presentations
Research poster created as part of Nursing 320 class. The poster examines the question, "Among the Alzheimer's disease population, does music therapy help enhance cognition compared to no treatment?"
Alzheimer's Dementia And Occupational Therapy, Sofia Demusaj, Averee Ortiz, Laura Swanson
Alzheimer's Dementia And Occupational Therapy, Sofia Demusaj, Averee Ortiz, Laura Swanson
Client Educational Handouts
This handout is an introduction to Alzheimer's dementia and the role that occupational therapy can have in the treatment of the disease. It contains facts, figures, signs, and symptoms of Alzheimer's dementia. It also contains examples of occupational therapy interventions and assessments for clients with Alzheimer's disease.
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
Cis-Regulatory Elements: Relevance For Alzheimer's Disease, Brianne Brazell Rogers
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disease, currently affecting more than six million Americans with limited treatment options. Identifying genetics contributors to neurodegenerative diseases has contributed critical insights into potential disease mechanisms. The majority of disease-associated genetic variants are located in non-coding regions, likely in regulatory elements, and affect the expression of target genes whose function contributes to neurodegeneration. Here, I performed a case-control study utilizing nuclei from dorsolateral prefrontal cortex postmortem tissue to correlate chromatin accessibility with gene expression and nominate 40,831 AD-specific candidate cis-regulatory elements. Additionally, work in this dissertation nominates ZEB1 and MAFB as candidate …
Palliative Performance Scale As A Prognostic Tool For Patients With Dementia In Hospice, Alexandria Nasr
Palliative Performance Scale As A Prognostic Tool For Patients With Dementia In Hospice, Alexandria Nasr
Scholarship in Medicine - All Papers
Objective: Palliative and hospice care have been shown to benefit people with dementia and their families. However, for patients with dementia who are nearing the end of life, hospice referral can be challenging because of the difficulty in predicting prognosis. The objective of this retrospective, exploratory study is two-fold: (1) to describe trajectories by analyzing trends in Palliative Performance Scale (PPS) scores for patients admitted to hospice with a neurocognitive disorder from time of enrollment to time of disenrollment and (2) to determine the relationship between PPS and length of stay (LOS) in hospice care.
Methods: The setting for the …
Ontario Neurodegenerative Disease Research Initiative (Ondri): Structural Mri Methods And Outcome Measures, Joel Ramirez, Melissa F. Holmes, Christopher J.M. Scott, Miracle Ozzoude, Miracle Ozzoude, Sabrina Adamo, Gregory M. Szilagyi, Maged Goubran, Fuqiang Gao, Stephen R. Arnott, Jane M. Lawrence-Dewar, Jane M. Lawrence-Dewar, Derek Beaton, Stephen C. Strother, Douglas P. Munoz, Mario Masellis, Richard H. Swartz, Robert Bartha, Sean P. Symons, Sandra E. Black, Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Sandra E. Black, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak
Ontario Neurodegenerative Disease Research Initiative (Ondri): Structural Mri Methods And Outcome Measures, Joel Ramirez, Melissa F. Holmes, Christopher J.M. Scott, Miracle Ozzoude, Miracle Ozzoude, Sabrina Adamo, Gregory M. Szilagyi, Maged Goubran, Fuqiang Gao, Stephen R. Arnott, Jane M. Lawrence-Dewar, Jane M. Lawrence-Dewar, Derek Beaton, Stephen C. Strother, Douglas P. Munoz, Mario Masellis, Richard H. Swartz, Robert Bartha, Sean P. Symons, Sandra E. Black, Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Sandra E. Black, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak
Medical Biophysics Publications
The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 years multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer's disease, mild cognitive impairment, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. The purpose …
Investigating A Multimodal Approach To Clinical Diagnosis Of Mild Cognitive Impairment And Alzheimer’S Disease, Sean M. Flannery
Investigating A Multimodal Approach To Clinical Diagnosis Of Mild Cognitive Impairment And Alzheimer’S Disease, Sean M. Flannery
Psychology Theses & Dissertations
An estimated 5.8 million Americans suffer from dementia due to Alzheimer’s disease (AD), with that number projected to grow to 13.8 million by mid-century (Alzheimer’s Association, 2019). Mild cognitive impairment (MCI) describes the stage between normal cognitive decline that comes with aging and a dementia diagnosis (Peterson, 1999). Due to a lack of a cure or particularly effective treatment, a major goal of treatment is to focus on improving quality of life (Budson & Solomon, 2016). An early and accurate diagnosis can address this goal in a variety of ways. Despite the high prevalence and immense amount of research in …
A Model Of Agitated Behavioral Symptoms In Persons With Alzheimer Disease, Katherine Kero
A Model Of Agitated Behavioral Symptoms In Persons With Alzheimer Disease, Katherine Kero
Wayne State University Dissertations
Background: Worldwide population trends are shifting with the population of Elders expected to dramatically increase in absolute and relative numbers in coming years. Alzheimer Disease (AD) is a common and costly disease of aging with agitation being the most poorly managed and detrimental behavioral symptom of the condition. The Nursing Theory of Unpleasant Symptoms provides a conceptual basis for understanding agitated behavioral symptoms associated with AD in the context of its antecedent causes and outcomes of the symptoms.
Purpose: The purpose of this dissertation was to model the predictors and outcomes of agitated behavioral symptoms in persons with AD. The …
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Perturbed Mitochondria-Er Contacts In Live Neurons That Model The Amyloid Pathology Of Alzheimer's Disease., Pamela V. Martino Adami, Zuzana Nichtova, David B. Weaver, Adam Bartok Dr., Thomas Wisniewski, Drew R. Jones, Sonia Do Carmo, Eduardo M. Castaño, A. Claudio Cuello, György Hajnóczky, Laura Morelli
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons.This article has an associated First Person interview with the first author of the paper.
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …
An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi
An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi
Pharmacology and Nutritional Sciences Faculty Publications
Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …
Combustion-Derived Nanoparticles, The Neuroenteric System, Cervical Vagus, Hyperphosphorylated Alpha Synuclein And Tau In Young Mexico City Residents, Lilian Calderón-Garcidueñas, Rafael Reynoso-Robles, Beatriz Pérez-Guillé, Partha S. Mukherjee, Angélica Gónzalez-Maciel
Combustion-Derived Nanoparticles, The Neuroenteric System, Cervical Vagus, Hyperphosphorylated Alpha Synuclein And Tau In Young Mexico City Residents, Lilian Calderón-Garcidueñas, Rafael Reynoso-Robles, Beatriz Pérez-Guillé, Partha S. Mukherjee, Angélica Gónzalez-Maciel
Mathematics Faculty Publications and Presentations
Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls. Electron microscopy of epithelial, endothelial and neural cells and immunoreactivity of stomach and vagus to phosphorylated ɑ-synuclein Ser129 and Hyperphosphorylated-Tau (Htau) …
Predicting Potential Alzheimer Medical Condition In Elderly Using Iot Sensors - Case Study, Zhi Hao Kevin Chong, Yu Xuan Tee, Ling Jing Toh, Shi Jia Phang, Jie Ying Liew, Bertran Queck, Swapna Gottipati
Predicting Potential Alzheimer Medical Condition In Elderly Using Iot Sensors - Case Study, Zhi Hao Kevin Chong, Yu Xuan Tee, Ling Jing Toh, Shi Jia Phang, Jie Ying Liew, Bertran Queck, Swapna Gottipati
Research Collection School Of Computing and Information Systems
Ageing population would cause profound problems and the impact is already being felt today in many developed countries such as Singapore. The main concern for the Government is to help the citizens with active ageing through home ownership and good healthcare. With Internet of Things (IoT) gaining traction globally, Singapore is set to take advantage of this technology and leverage it to extend its capabilities towards a graceful Ageing-In-Place for the elderly. This ties in nicely with the expertise of SHINE Seniors project by SMU-iCity Lab, which integrates IT with healthcare in ways that creates innovative IT health solutions that …
Network Exploration Of Correlated Multivariate Protein Data For Alzheimer's Disease Association, Matthew J. Lane
Network Exploration Of Correlated Multivariate Protein Data For Alzheimer's Disease Association, Matthew J. Lane
Theses
Alzheimer Disease (AD) is difficult to diagnose by using genetic testing or other traditional methods. Unlike diseases with simple genetic risk components, there exists no single marker determining as to whether someone will develop AD. Furthermore, AD is highly heterogeneous and different subgroups of individuals develop the disease due to differing factors. Traditional diagnostic methods using perceivable cognitive deficiencies are often too little too late due to the brain having suffered damage from decades of disease progression. In order to observe AD at early stages prior to the observation of cognitive deficiencies, biomarkers with greater accuracy are required. By using …
Alterations In Erythrocyte Fatty Acid Composition In Preclinical Alzheimer's Disease, Kathryn Goozee, Pratishtha Chatterjee, Ian James, Kaikai Shen, Hamid R. Sohrabi, Prita R. Ash, Preeti Dave, Bethany Ball, Candice Manyan, Kevin Taddei, Roger Chung, Manohar L. Garg, Ralph Martins
Alterations In Erythrocyte Fatty Acid Composition In Preclinical Alzheimer's Disease, Kathryn Goozee, Pratishtha Chatterjee, Ian James, Kaikai Shen, Hamid R. Sohrabi, Prita R. Ash, Preeti Dave, Bethany Ball, Candice Manyan, Kevin Taddei, Roger Chung, Manohar L. Garg, Ralph Martins
Research outputs 2014 to 2021
Brain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65 – 90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a ‘base model’ comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our …
Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha
Bladder Antimuscarinics And Cognitive Decline In Elderly Patients, Daniela Claudia Moga, Erin L. Abner, Qishan Wu, Gregory A. Jicha
Pharmacy Practice and Science Faculty Publications
Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent.
Methods: A retrospective analysis of data from the National Alzheimer's Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores.
Results: Our analyses included 698 …
Forget-Me-Not, Daniel Barber-Cironi, Shawn Nicholson, Jake Kruse, Nicole Dent
Forget-Me-Not, Daniel Barber-Cironi, Shawn Nicholson, Jake Kruse, Nicole Dent
Williams Honors College, Honors Research Projects
The purpose of Forget-Me-Not is to provide another level of care and comfort to those suffering from mild dementia, as well as provide further assistance for a friend, family member, or caretaker who may look after them. Research shows that timely reminders and persistent information can greatly improve the quality of life for those afflicted with mild dementia (Mokhtari et al.). Forget-Me-Not’s persistent display and wearable smart-bracelet offer a customizable and well connected system to provide these reminders. For the caretaker, a mobile application is provided in order to maintain the display and notify them of emergencies or critical events …
Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra
Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra
Sanders-Brown Center on Aging Faculty Publications
One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads …
Beneficial Effects Of Increased Lysozyme Levels In Alzheimer's Disease Modelled In Drosophila Melanogaster, Linnea Sandin, Liza Bergkvist, Sangeeta Nath, Claudia Kielkopf, Camilla Janefjord, Linda Helmfors, Henrik Zetterberg, Kaj Blennow, Hongyun Li, Camilla Nilsberth, Brett Garner, Ann-Christin Brorsson, Katarina Kagedal
Beneficial Effects Of Increased Lysozyme Levels In Alzheimer's Disease Modelled In Drosophila Melanogaster, Linnea Sandin, Liza Bergkvist, Sangeeta Nath, Claudia Kielkopf, Camilla Janefjord, Linda Helmfors, Henrik Zetterberg, Kaj Blennow, Hongyun Li, Camilla Nilsberth, Brett Garner, Ann-Christin Brorsson, Katarina Kagedal
Illawarra Health and Medical Research Institute
Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer's disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme …
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
Impairment Of The Gliovascular Unit In Neurological Disease, Ian Kimbrough
All ETDs from UAB
Cerebral blood flow is regulated by vasoactive molecules released by astroglial cell processes that ensheath the entire cerebrovasculature. This regulation of blood flow in response to neuronal activity is a process known as functional hyperemia. Astrocytes, along with their associated neurons and microvessels, are organized into a functional system called the gliovascular unit (GVU). The astroglial component of the GVU is integral in both regulation of blood flow and maintenance of the blood-brain barrier (BBB). In disease, this system can be disrupted. We found that glioma cells displace astrocytic processes, called endfeet, and prevent their communication with associated vessels, leading …
Correlation Of Amyloid Beta And Spatial Learning And Memory Deficits On A Thy1-App Mouse Model For Alzheimer's Disease, Amber Lynn Betz
Correlation Of Amyloid Beta And Spatial Learning And Memory Deficits On A Thy1-App Mouse Model For Alzheimer's Disease, Amber Lynn Betz
Theses and Dissertations - UTB/UTPA
The McGill-Thy1 APP mouse is a triple transgenic model of Alzheimer disease, which has the mutant amyloid precursor protein to synergistically over-produce amyloid beta plaques. These mice exhibit visuo-spatial learning impairment at 3 months of age and memory impairment at 10-13 months of age in the Morris water maze. To extend these findings mice at 3, 5, and 7 months of age were tested on the Barnes maze. Non-Transgenic and Transgenic mice showed improvement during acquisition. However, 3 month and 5 month McGill Thy1- APP mice showed impaired acquisition learning while 7 month showed a learning and memory deficit compared …
Political Drive To Screen For Pre-Dementia: Not Evidence Based And Ignores The Harms Of Diagnosis, David Le Couteur, Jenny A. Doust, Helen Creasey, Carol Brayne
Political Drive To Screen For Pre-Dementia: Not Evidence Based And Ignores The Harms Of Diagnosis, David Le Couteur, Jenny A. Doust, Helen Creasey, Carol Brayne
Jenny Doust
Current policy in many countries is aimed at increasing the rates of diagnosis of dementia and cognitive impairment.1 2 3 This policy drive has been accompanied by research into early detection of dementia, including preclinical identification of underlying neurobiology that might later be associated with dementia.4 Although the clinical features of people with established dementia are unmistakable,5 6 the ability of these preclinical features to predict future disease is less clear. Nevertheless, the belief that there is value in screening for “pre-dementia” or mild cognitive impairment is creeping into clinical practice, with the resulting overdiagnosis having potential adverse consequences for …
Tau-Sh3 Interactions: Implications For Alzheimer's Disease, Jesse Nicholas Cochran
Tau-Sh3 Interactions: Implications For Alzheimer's Disease, Jesse Nicholas Cochran
All ETDs from UAB
Alzheimer’s disease (AD) is the most common neurodegenerative disease and with Americans’ increasing longevity it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-beta, but the optimal strategy for targeting tau has not yet been identified. Based on considerable preclinical data from AD models, we hypothesize that interactions between tau and SH3 domain–containing proteins are pathogenic in AD. Genetically reducing either tau or tau interactants has beneficial effects relevant to AD. Here, we describe a drug screen for …
Nutrition And Prevention Of Alzheimer's Dementia, Arun Swaminathan, Gregory A. Jicha
Nutrition And Prevention Of Alzheimer's Dementia, Arun Swaminathan, Gregory A. Jicha
Neurology Faculty Publications
A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may …
Detection Of Bacterial Antigens And Alzheimer's Disease-Like Pathology In The Central Nervous System Of Balb/C Mice Following Intranasal Infection With A Laboratory Isolate Of Chlamydia Pneumoniae, C. Scott Little Phd, Timothy A. Joyce, Christine Hammond, Hazem Matta, David Cahn, Denah Appelt, Brian J. Balin Phd
Detection Of Bacterial Antigens And Alzheimer's Disease-Like Pathology In The Central Nervous System Of Balb/C Mice Following Intranasal Infection With A Laboratory Isolate Of Chlamydia Pneumoniae, C. Scott Little Phd, Timothy A. Joyce, Christine Hammond, Hazem Matta, David Cahn, Denah Appelt, Brian J. Balin Phd
PCOM Scholarly Papers
Pathology consistent with that observed in Alzheimer’s disease (AD) has previously been documented following intranasal infection of normal wild-type mice with Chlamydia pneumoniae (Cpn) isolated from an AD brain (96-41). In the current study, BALB/c mice were intranasally infected with a laboratory strain of Cpn, AR-39, and brain and olfactory bulbs were obtained at 1-4 months post-infection (pi). Immunohistochemistry for amyloid beta or Cpn antigens was performed on sections from brains of infected or mock-infected mice. Chlamydia-specific immunolabeling was identified in olfactory bulb tissues and in cerebrum of AR-39 infected mice. The Cpn specific labeling was most prominent at 1 …
Clinical Trials And Late-Stage Drug Development In Alzheimer’S Disease: An Appraisal From 1984 To 2014, L. S. Schneider, F. Mangialasche, S. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, M. Kivipelto
Clinical Trials And Late-Stage Drug Development In Alzheimer’S Disease: An Appraisal From 1984 To 2014, L. S. Schneider, F. Mangialasche, S. Andreasen, H. Feldman, E. Giacobini, R. Jones, V. Mantua, P. Mecocci, L. Pani, B. Winblad, M. Kivipelto
Human Clinical Trials Collection
The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30 years, considering the drugs, …
Amyloid Β Peptides Modify The Expression Of Antioxidant Repair Enzymes And A Potassium Channel In The Septohippocampal System, Jorge Duran-Gonzalez, Edna D. Michi, Brisa Elorza, Miriam G. Perez-Cordova, Luis F. Pacheco Otalora, Ahmed Touhami, Pamela Paulson, George Perry, Ian V. Murray, Luis V. Colom
Amyloid Β Peptides Modify The Expression Of Antioxidant Repair Enzymes And A Potassium Channel In The Septohippocampal System, Jorge Duran-Gonzalez, Edna D. Michi, Brisa Elorza, Miriam G. Perez-Cordova, Luis F. Pacheco Otalora, Ahmed Touhami, Pamela Paulson, George Perry, Ian V. Murray, Luis V. Colom
Health & Biomedical Sciences Faculty Publications and Presentations
Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder characterized by extracellular accumulations of amyloid β (Aβ) peptides, intracellular accumulation of abnormal proteins, and early loss of basal forebrain neurons. Recent studies have indicated that the conformation of Aβ is crucial for neuronal toxicity, with intermediate misfolded forms such as oligomers being more toxic than the final fibrillar forms. Our previous work shows that Aβ blocks the potassium (K(+)) currents IM and IA in septal neurons, increasing firing rates, diminishing rhythmicity and firing coherence. Evidence also suggests that oxidative stress (OS) plays a role in AD pathogenesis. Thus we wished …
Neurotrophin Signaling And Alzheimer's Disease Neurodegeneration - Focus On Bdnf/Trkb Signaling, Jenny Wong
Neurotrophin Signaling And Alzheimer's Disease Neurodegeneration - Focus On Bdnf/Trkb Signaling, Jenny Wong
Illawarra Health and Medical Research Institute
Neurotrophins are small proteins vital for neuronal growth, differentiation, survival, and plasticity. Members of the mammalian neurotrophin family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin- 4/5 (NT-4/5). Their neurotrophic effects are mediated by the tropomyosin receptor kinase (Trk) receptors, membrane-bound receptor tyrosine kinases (NGF for TrkA, BDNF and NT4/5 for TrkB, and NT-3 for TrkC) which activate various cell signaling pathways linked to growth, differentiation, and survival. The importance of neurotrophin signaling in brain development is highlighted by findings showing that knockout mice for any one of the neurotrophins or their receptors are fatal …
Deletion Of Abca7 Increases Cerebral Amyloid-Β Accumulation In The J20 Mouse Model Of Alzheimer's Disease, Woojin S. Kim, Hongyun Li, Kalani Ruberu, Sharon Chan, David A. Elliott, Jac Kee Low, David Cheng, Tim Karl, Brett Garner
Deletion Of Abca7 Increases Cerebral Amyloid-Β Accumulation In The J20 Mouse Model Of Alzheimer's Disease, Woojin S. Kim, Hongyun Li, Kalani Ruberu, Sharon Chan, David A. Elliott, Jac Kee Low, David Cheng, Tim Karl, Brett Garner
Faculty of Science, Medicine and Health - Papers: part A
ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and has been detected in macrophages, microglia, and neurons. ABCA7 promotes efflux of lipids from cells to apolipoproteins and can also regulate phagocytosis and modulate processing of amyloid precursor protein (APP) to generate the Alzheimer's disease (AD) amyloid-β (Aβ) peptide. Genome-wide association studies have indicated that ABCA7 single nucleotide polymorphisms confer increased risk for late-onset AD; however, the role that ABCA7 plays in the brain in the AD context is unknown. In the present study, we crossed ABCA7-deficient (A7-/-) mice with J20 amyloidogenic mice to address this issue. We show …
Brain Immune Interactions And Air Pollution: Macrophage Inhibitory Factor (Mif), Prion Cellular Protein (Prpc), Interleukin-6 (Il-6), Interleukin 1 Receptor Antagonist (Il-1ra), And Interleukin-2 (Il-2) In Cerebrospinal Fluid And Mif In Serum Differentiate Urban Children Exposed To Severe Vs. Low Air Pollution, Lilian Calderón-Garcidueñas, Janet V. Cross, Maricela Franco-Lira, Mariana Aragón-Flores, Michael Kavanaugh, Ricardo Torres-Jardon, Chih-Kai Chao, Charles Thompson, Jing Chang, Hongtu Zhu, Amedeo D'Angiulli
Brain Immune Interactions And Air Pollution: Macrophage Inhibitory Factor (Mif), Prion Cellular Protein (Prpc), Interleukin-6 (Il-6), Interleukin 1 Receptor Antagonist (Il-1ra), And Interleukin-2 (Il-2) In Cerebrospinal Fluid And Mif In Serum Differentiate Urban Children Exposed To Severe Vs. Low Air Pollution, Lilian Calderón-Garcidueñas, Janet V. Cross, Maricela Franco-Lira, Mariana Aragón-Flores, Michael Kavanaugh, Ricardo Torres-Jardon, Chih-Kai Chao, Charles Thompson, Jing Chang, Hongtu Zhu, Amedeo D'Angiulli
Biomedical and Pharmaceutical Sciences Faculty Publications
Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile …