Medicine and Health Sciences Commons^™

Editorial: Neurotoxins In Alzheimer's Disease And Other Dementias, Alexandre Henriques, Philippe L. L. Poindron, Binosha Fernando, Kevin N. Hascup

Research outputs 2022 to 2026

Alzheimer's disease (AD) and other dementias are neurodegenerative disorders characterized by a progressive decline in cognition and independence from activities of daily living. Dementia is multifactorial with numerous risk factors including age, genes, molecules, lifestyle, and environmental contributions to disease onset and progression. In recent years, an emerging focus on neurotoxins has added a new layer of complexity to our understanding of dementia. This editorial aims to discuss recent updates regarding the role of neurotoxins in the pathogenesis of dementia.

Plasma Glial Fibrillary Acidic Protein In Autosomal Dominant Alzheimer's Disease: Associations With Aβ-Pet, Neurodegeneration, And Cognition, Pratishtha Chatterjee, Lisa Vermunt, Brian A. Gordon, Steve Pedrini, Lynn Boonkamp, Nicola J. Armstrong, Chengjie Xiong, Abhay K. Singh, Yan Li, Hamid R. Sohrabi, Kevin Taddei, Mark Molloy, Tammie L. S. Benzinger, John C. Morris, Celeste Karch, Sarah Berman, Jasmeer Chhatwal, Carlos Cruchaga, Neill R. Graff-Radford, Gregory S. Day, Martin Farlow, Nick Fox, Alison Goate, Jason Hassenstab, Jae-Hong Lee, Johannes Levin, Eric Mcdade, Hiroshi Mori, Richard Perrin, Raquel Sanchez-Valle, Peter R. Schofield, Allan Levey, Mathias Jucker, Colin L. Masters, Anne M. Fagan, Randall J. Bateman, Ralph N. Martins, Charlotte Teunissen, Dominantly Inherited Alzheimer Network

Research outputs 2022 to 2026

Background: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. Methods: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Results: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (A ) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished A -positive from A -negative ADAD …

Longitudinal Trajectories Of Basal Forebrain Volume In Normal Aging And Alzheimer's Disease, Ying Xia, Paul Maruff, Vincent Doré, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp

Research outputs 2022 to 2026

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid- (A ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed A -PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and A status (A −, A +). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high A …

Physical Activity And Brain Amyloid Beta: A Longitudinal Analysis Of Cognitively Unimpaired Older Adults, Michael G. Slee, Stephanie R. Rainey-Smith, Victor L. Villemagne, James D. Doecke, Hamid R. Sohrabi, Kevin Taddei, David Ames, Vincent Dore, Paul Maruff, Simon M. Laws, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Kirk I. Erickson, Belinda M. Brown

Research outputs 2022 to 2026

Introduction: The current study evaluated the relationship between habitual physical activity (PA) levels and brain amyloid beta (A ) over 15 years in a cohort of cognitively unimpaired older adults. Methods: PA and A measures were collected over multiple timepoints from 731 cognitively unimpaired older adults participating in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Aging. Regression modeling examined cross-sectional and longitudinal relationships between PA and brain A . Moderation analyses examined apolipoprotein E (APOE) 4 carriage impact on the PA-A relationship. Results: PA was not associated with brain A at baseline ( = –0.001, p = 0.72) …

Rna Editing Of Microtubule-Associated Protein Tau Circular Rnas Promotes Their Translation And Tau Tangle Formation, Justin Ralph Welden, Giorgi Margvelani, Karol Andrea Arizaca Maquera, Bhavani Gudlavalleti, Sandra C. Miranda Sardón, Alexandre Rosa Campos, Noémie Robil, Daniel C. Lee, Alvaro G. Hernandez, Wang-Xia Wang, Jing Di, Pierre De La Grange, Peter T. Nelson, Stefan Stamm

Sanders-Brown Center on Aging Faculty Publications

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1–R4. For the 12→10 circRNA, a start codon can be introduced by two …

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

The Trend Of Disruption In The Functional Brain Network Topology Of Alzheimer’S Disease, Alireza Fathian, Yousef Jamali, Mohammad Reza Raoufy, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Norbert Schuf, Howard J. Rosen, Bruce L. Miller, Thomas Neylan, Jacqueline Hayess, Shannon Finley, Paul Aisen, Zaven Khachaturian, Ronald G. Thomas, Charles D. Smith, Gregory A. Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brain’s functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimer’s disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and …

Sex Differences In The Genetic Architecture Of Cognitive Resilience To Alzheimer’S Disease, Jaclyn M. Eissman, Logan Dumitrescu, Emily R. Mahoney, Alexandra N. Smith, Shubhabrata Mukherjee, Michael L. Lee, Phoebe Scollard, Seo Eun Choi, William S. Bush, Corinne D. Engelman, Qiongshi Lu, David W. Fardo, Emily H. Trittschuh, Jesse Mez, Catherine C. Kaczorowski, Hector Hernandez Saucedo, Keith F. Widaman, Rachel F. Buckley, Michael J. Properzi, Elizabeth C. Mormino, Hyun Sik Yang, Theresa M. Harrison, Trey Hedden, Kwangsik Nho, Shea J. Andrews, Douglas Tommet, Niran Hadad, R. Elizabeth Sanders, Douglas M. Ruderfer, Katherine A. Gifford, Xiaoyuan Zhong, Neha S. Raghavan, Badri Vardarajan, Margaret A. Pericak-Vance, Lindsay A. Farrer, Li San Wang, Carlos Cruchaga, Gerard D. Schellenberg, Nancy J. Cox, Jonathan L. Haines, C. Dirk Keene, Andrew J. Saykin, Eric B. Larson, Reisa A. Sperling, Richard Mayeux, Michael L. Cuccaro, David A. Bennett, Julie A. Schneider, Paul K. Crane, Angela L. Jefferson, Timothy J. Hohman

Sanders-Brown Center on Aging Faculty Publications

Approximately 30% of elderly adults are cognitively unimpaired at time of death despite the presence of Alzheimer's disease neuropathology at autopsy. Studying individuals who are resilient to the cognitive consequences of Alzheimer's disease neuropathology may uncover novel therapeutic targets to treat Alzheimer's disease. It is well established that there are sex differences in response to Alzheimer's disease pathology, and growing evidence suggests that genetic factors may contribute to these differences. Taken together, we sought to elucidate sex-specific genetic drivers of resilience.

We extended our recent large scale genomic analysis of resilience in which we harmonized cognitive data across four cohorts …

Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse

Faculty Scholarship

U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

New Insights Into The Genetic Etiology Of Alzheimer’S Disease And Related Dementias, Céline Bellenguez, Fahri Küçükali, Iris Jansen, Luca Kleineidam, Sonia Moreno-Grau, Najaf Amin, Adam C. Naj, Rafael Campos-Martin, David W. Fardo, Yuriko Kastumata, Erin L. Abner, Radb, Gr@Ace, Degesco, Eadi, Gerad, Demgene, Finngen, Adgc, Charge

Sanders-Brown Center on Aging Faculty Publications

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly …

Investigating The Mitochondrial Protein Mitoneet In C. Elegans Models Of Aging And Alzheimer's Disease, Jacob Ryan Boos

Graduate Theses, Dissertations, and Problem Reports

Oxidative stress is an imbalance between reactive oxygen species production and elimination, favoring the former. Reactive oxygen species serve as important signaling molecules for physiological homeostasis. However, when produced in excess, these once important signaling molecules become detrimental, disrupting cellular functions, and ultimately leading to cell death. In aging, reactive oxygen species production is increased, accompanied with reductions in oxidative stress resistance, increasing the risk for developing age-related diseases including cardiovascular disease, cancer, stroke, and neurodegenerative diseases. The outer mitochondrial membrane iron-sulfur cluster containing protein mitoNEET (CISD1; gene CISD1) has shown to be a mediator of mitochondrial function and …

Using Imputation To Provide Harmonized Longitudinal Measures Of Cognition Across Aibl And Adni, Rosita Shishegar, Timothy Cox, David Rolls, Pierrick Bourgeat, Vincent Doré, Fiona Lamb, Joanne Robertson, Simon M. Laws, Tenielle Porter, Jurgen Fripp, Duygu Tosun, Paul Maruff, Greg Savage, Christopher C. Rowe, Colin L. Masters, Michael W. Weiner, Victor L. Villemagne, Samantha C. Burnham

Research outputs 2014 to 2021

To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning …

Random Forest-Integrated Analysis In Ad And Late Brain Transcriptome-Wide Data To Identify Disease-Specific Gene Expression, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects thinking, memory, and behavior. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently identified common neurodegenerative disease that mimics the clinical symptoms of AD. The development of drugs to prevent or treat these neurodegenerative diseases has been slow, partly because the genes associated with these diseases are incompletely understood. A notable hindrance from data analysis perspective is that, usually, the clinical samples for patients and controls are highly imbalanced, thus rendering it challenging to apply most existing machine learning algorithms to directly analyze such datasets. Meeting this data analysis challenge is …

Q134r: Small Chemical Compound With Nfat Inhibitory Properties Improves Behavioral Performance And Synapse Function In Mouse Models Of Amyloid Pathology, Pradoldej Sompol, Jenna L. Gollihue, Susan D. Kraner, Irina A. Artiushin, Ryan A. Cloyd, Emad Chishti, Shon A. Koren, Grant K. Nation, Jose F. Abisambra, Orsolya Huzian, Lajos I. Nagy, Miklos Santha, Laszlo Hackler Jr., Laszlo G. Puskas, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. …

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

Alzheimer’S And Patient Caregiver Burnout: A Comprehensive Review Of The Literature, Madeline J. Hekeler

Senior Honors Projects, 2020-current

The term ‘silent epidemic’ has become fitting for Alzheimer’s disease, as it is now the sixth leading cause of death in the US. Caring for AD patients at home in the US costs billions of dollars each year. The current comprehensive literature review discusses the background/history of AD, pathology and modes of transmission of AD, behavioral and natural risk factors, prevention and treatment options, and how the aforementioned factors contribute to caregiver burnout and subsequently affect the AD patient. The extensive examination of the literature determined several gaps to be addressed. More specifically, burnout among AD caregivers has become an …

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …

Investigating Diffusion Tensor Imaging Correlates Of Cognitive Impairment In Idiopathic Normal Pressure Hydrocephalus And Alzheimer's Disease, Omar Hasan, Omar Hasan

Dissertations & Theses (Open Access)

Modest expansion of the human brain cerebrospinal fluid (CSF)-filled ventricles is normal with aging, and because of this, it can be difficult for physicians to accurately diagnose and treat enlarged ventricles (ventriculomegaly), called hydrocephalus¹ (fluid or water in the brain) Ventriculomegaly occurs due to an obstruction (such as a blood clot or tumor), or a change in CSF absorption². Primary hydrocephalus, also called idiopathic normal pressure hydrocephalus (iNPH), is non-obstructive and may be comorbid with other neurodegenerative diseases such as Alzheimer’s disease (AD) or frontotemporal dementia (FTD). Clinically, it can be difficult to tell whether the pathophysiological …

Spon1 Is Associated With Amyloid-Β And Apoe Ε4-Related Cognitive Decline In Cognitively Normal Adults, Shane Fernandez, Samantha C. Burnham, Lidija Milicic, Greg Savage, Paul Maruff, Madeline Peretti, Hamid R. Sohrabi, Yen Ying Lim, Michael Weinborn, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, David Groth, Giuseppe Verdile, Victor L. Villemagne, Tenielle Porter, Simon M. Laws

Research outputs 2014 to 2021

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β …

Polygenic Score Modifies Risk For Alzheimer's Disease In Ε4 Homozygotes At Phenotypic Extremes, Aamira J. Huq, Brian Fulton-Howard, Moeen Riaz, Simon Laws, Robert Sebra, Joanne Ryan, Alzheimer’S Disease Genetics Consortium, Alan E. Renton, Alison M. Goate, Colin L. Masters, Elsdon Storey, Raj C. Shah, Anne Murray, John Mcneil, Ingrid Winship, Paul A. Jones

Research outputs 2014 to 2021

Introduction: Diversity in cognition among apolipoprotein E () ε4 homozygotes can range from early-onset Alzheimer's disease (AD) to a lifetime with no symptoms. Methods: We evaluated a phenotypic extreme polygenic risk score (PRS) for AD between cognitively healthy ε4 homozygotes aged ≥75 years (n = 213) and early-onset ε4 homozygote AD cases aged ≤65 years (n = 223) as an explanation for this diversity. Results: The PRS for AD was significantly higher in ε4 homozygote AD cases compared to older cognitively healthy ε4/ε4 controls (odds ratio [OR] 8.39; confidence interval [CI] 2.0-35.2; = .003). The difference in the same PRS …

Intake Of Products Containing Anthocyanins, Flavanols, And Flavanones, And Cognitive Function: A Narrative Review, Samantha L. Gardener, Stephanie R. Rainey-Smith, Michael Weinborn, Catherine P. Bondonno, Ralph N. Martins

Research outputs 2014 to 2021

The purpose of this review is to examine human research studies published within the past 6 years which evaluate the role of anthocyanin, flavanol, and flavanone consumption in cognitive function, and to discuss potential mechanisms of action underlying any observed benefits. Evidence to date suggests the consumption of flavonoid-rich foods, such as berries and cocoa, may have the potential to limit, or even reverse, age-related declines in cognition. Over the last 6 years, the flavonoid subgroups of anthocyanins, flavanols, and flavanones have been shown to be beneficial in terms of conferring neuroprotection. The mechanisms by which flavonoids positively modulate cognitive …

Potential Of Sorghum Polyphenols To Prevent And Treat Alzheimer's Disease: A Review Article, Nasim Rezaee, Warnakulasuriya Mary Ann Dipika Fernando, Eugene Hone, Hamid R. Sohrabi, Stuart K. Johnson, Stuart Gunzburg, Ralph Martins

Research outputs 2014 to 2021

Alzheimer’s disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a …

The Support Person's Preferences And Perspectives Of Physical Activity Programs For Older Adults With Cognitive Impairment, Terence W. H. Chong, Emily You, Kathryn A. Ellis, Kay L. Cox, Karra D. Harrington, Stephanie R. Rainey-Smith, David Ames, Nicola T. Lautenschlager, Aibl Research Group

Research outputs 2014 to 2021

Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms …

Investigating Auditory Electrophysiological Measures Of Participants With Mild Cognitive Impairment And Alzheimer's Disease: A Systematic Review And Meta-Analysis Of Event-Related Potential Studies, Hadeel Y. Tarawneh, Wilhelmina H. A. M. Mulders, Hamid R. Sohrabi, Ralph N. Martins, Dona M. P. Jayakody

Research outputs 2014 to 2021

Background: Objectively measuring auditory functions has been proposed as an avenue in differentiating normal age-related cognitive dysfunction from Alzheimer's disease (AD) and its prodromal states. Previous research has suggested auditory event-related potentials (AERPs) to be non-invasive, cost-effective, and efficient biomarkers for the diagnosis of AD. Objective: The objective of this paper is to review the published literature on AERPs measures in older adults diagnosed with AD and those at higher risk of developing AD, i.e., mild cognitive impairment (MCI) and subjective cognitive decline. Methods: The search was performed on six major electronic databases (Ovid MEDLINE, OVID EMBASE, PsycINFO, PubMed, Scopus, …

Fifteen Years Of The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study: Progress And Observations From 2,359 Older Adults Spanning The Spectrum From Cognitive Normality To Alzheimer's Disease, Christopher Fowler, Stephanie R. Rainey-Smith, Sabine Bird, Julia Bomke, Pierrick Bourgeat, Belinda M. Brown, Samantha C. Burnham, Ashley I. Bush, Carolyn Chadunow, Steven Collins, James Doecke, Vincent Doré, Kathryn A. Ellis, Lis Evered, Amir Fazlollahi, Jurgen Fripp, Samantha L. Gardener, Simon Gibson, Robert Grenfell, Elise Harrison, Richard Head, Liang Jin, Adrian Kamer, Fiona Lamb, Nicola T. Lautenschlager, Simon M. Laws, Qiao-Xin Li, Lucy Lim, Yen Ying Lim, Andrea Louey, S. Lance Macaulay, Lucy Mackintosh, Ralph N. Martins, Paul Maruff, Colin L. Masters, Simon Mcbride, Lidija Milicica, Madeline Peretti, Kelly Pertile, Tenielle Porter, Morgan Radler, Alan Rembach, Joanne Robertson, Mark Rodrigues, Christopher C. Rowe, Rebecca Rumble, Olivier Salvado, Greg Savage, Brendan Silbert, Magdalene Soh, Hamid R. Sohrabi, Kevin Taddei, Tania Taddei, Christine Thai, Brett Trounson, Regan Tyrrell, Michael Vacher, Shiji Varghese, Victor L. Villemagne, Michael Weinborn, Michael Woodward, Ying Xia, David Ames, Aibl Investigators

Research outputs 2014 to 2021

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance …

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

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

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

USF Tampa Graduate Theses and Dissertations

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

Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.

Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.

Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …

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

Brain and Mind Institute Researchers' Publications

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

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

Sanders-Brown Center on Aging Faculty Publications

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