Neurosciences Commons^™

Genome-Wide Association Study Identifies Novel Variants In Olfactory, Vitamin A, Vitamin B, And Cadherin Pathways Associated With Learning And Memory, Lloyd N. Hopkins, Nesli Avgan, Heidi G. Sutherland, Francesca E. Fernandez, Emma M. Knowles, Larisa M. Haupt, John Blangero, David C. Glahn, David H. K. Shum, Rod A. Lea, Lyn R. Griffiths

Human Genetics Publications

Learning and memory, as fundamental components of human cognition, are heritable traits that are highly variable between individuals and within populations. Investigation into the genetic basis of cognition is a prominent area of research, with genetic associations being previously reported for a wide range of cognitive phenotypes. Here we utilise a genome-wide association study (GWAS) approach to evaluate the contribution of genetic variation to learning and memory phenotypes in a comprehensively phenotyped, well-characterised, healthy, and unrelated cohort of individuals (n = 613). Cognitive phenotypes were assessed using nine comprehensive test batteries consisting of twenty-one cognitive performance assessments including IQ, five …

Rare Heterozygous De Novo Variants In Rapgef2 Are Associated With A Neurodevelopmental Disorder, Ali H Bereshneh, Kirkland A Wilson, Xueyang Pan, Shabab B Hannan, Megan A Cooper, Jullianne Diaz, Eyby Leon, Tiana M Moses, Mahshid S Azamian, Daryl A Scott, Ping Yee Billie Au, Juan Pablo Appendino, Ingrid E Scheffer, Antony Kaspi, Melanie Bahlo, Michael S Hildebrand, Angela T Morgan, Ekanem Ekure, Joshua M Shulman, Friedhelm Hildebrandt, Jennifer E Posey, Paul Kruszka, Eric Vilain, Shinya Yamamoto, Oguz Kanca, Seth Berger, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: RAPGEF2 encodes a guanine nucleotide exchange factor (GEF) that activates small GTPases and has not been linked to a Mendelian disorder. RAPGEF2 is highly intolerant to loss-of-function variants. We report 5 de novo heterozygous variants in RAPGEF2 in unrelated individuals with developmental delay, attention deficit hyperactivity disorder, epilepsy, dysmorphic features, or other manifestations. We used a Drosophila model to assess the functional impact of the identified human variants.

Methods: We generated a Kozak-GAL4 null allele of the Drosophila ortholog of RAPGEF2, PDZ-GEF, and used the allele to determine the gene expression pattern as well as the loss-of-function phenotypes. We …

The Role Of Isotocin In Female Zebrafish (Danio Rerio) Reproductive Behavior And Its Implication For Intranasal Oxytocin Therapy In Humans, Katelynn M. Benge

Masters Theses

In the past several decades, oxytocin has been colloquially termed the “cuddle hormone,” due to its role in pair-bonding and monogamy (Carter et al., 1992). In addition to being used experimentally for psychological disorder, it has also been used in couple’s counseling settings (Anagnostou et al., 2014; Domes et al., 2016). The outcomes of this research reveal mixed results, creating a need for further research in the topic to understand the exact mechanisms by which oxytocin works in the brain to induce this prosocial response. This study sought to address this deficit through the zebrafish animal model. The zebrafish serves …

Task-Optimized Brain Parcellations Reveal Latent Functional Organization For Enhanced Connectivity-Based Neuroimaging Classification, Andrew Hannum, Mario A. Lopez

Computer Science: Faculty Scholarship

Brain parcellation schemes are fundamental to neuroimaging, yet general-purpose atlases may obscure the specific functional architecture relevant to a given cognitive task or clinical condition. This reflects a growing consensus that the “optimal” brain map is context-dependent. Here, we introduce a novel framework that validates this principle by generating task-optimized human brain parcellation maps directly from supervised learning objectives. Our method defines functional parcels by grouping brain regions based on the similarity of their contributions to a classifier's decision boundary for a specific goal (e.g., cognitive state decoding or clinical group separation). This approach prioritizes a region's discriminative role over …

Pathogenesis Of Polyglutamine Diseases: Piecing Together A Complex Molecular Puzzle, Esmeralda Villavicencio Gonzalez, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

Dark And Camouflaged Genomic Regions Remain Challenging In Chm13, Mark E. Wadsworth, Madeline L. Page, Bernardo Aguzzoli Heberle, Justin B. Miller, Cody J. Steely, Mark T. W. Ebbert

Sanders-Brown Center on Aging Faculty Publications

Comprehensive genomic analysis is essential for advancing our understanding of human genetics and disease. However, short-read sequencing technologies are inherently limited in their ability to resolve highly repetitive, structurally complex, and low-mappability genomic regions, previously coined as “dark” regions. Long-read sequencing technologies, such as PacBio and Oxford Nanopore Technologies (ONT), offer improved resolution of these regions, yet they are not perfect. With the advent of the new Telomere-to-Telomere (T2T) CHM13 reference genome, exploring its effect on dark regions is prudent. In this study, we systematically analyze dark regions across four human genome references—HG19, HG38 (with and without alternate contigs), and …

Data-Driven Thresholds For Standardized Classification Of Severe Alzheimer’S Disease Neuropathology Using Digital Neuropathology, Ryan K. Shahidehpour, Allison M. Neltner, Mitchell A. Klusty, Cole Corbett, Angelique D. Gonzalez, David A. Gutman, David W. Fardo, Adam D. Bachstetter, Cody Bumgardner, Margaret E. Flanagan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Alzheimer's disease neuropathological changes (ADNC)—operationalized with semi-quantitative parameters—represent the consensus-based gold standard for diagnostic evaluation of disease severity. Although useful, ADNC diagnostic frameworks have limitations, particularly in advanced disease stages where pathological severity varies widely within a given diagnostic category. Further, some individuals lacking cognitive impairment are inappropriately categorized as having severe ADNC. In this study, quantitative pathology metrics and alternative tissue sampling schemes were integrated with data about premortem cognitive status, in order to derive clinically informed neuropathologic diagnostic thresholds. Specific goals of the current study were to generate data-driven, standardized diagnostic cut-points, with the most severe stages of …

Clonal Expansion Of Cytotoxic Cd8⁺ T Cells In Lecanemab-Associated Aria, Lance A. Johnson, Kai Saito, Akhil V. Pallerla, Jessica L. Funnell, Ashley R. Ezzo, Chelsea M. Song, Douglas A. Harrison, Noah J. Norton, Lauren C. Moore, Linda J. Van Eldik, David W. Fardo, Greg E. Cooper, Josh M. Morganti

Sanders-Brown Center on Aging Faculty Publications

Amyloid-related imaging abnormalities (ARIA) are the principal safety concern limiting anti-amyloid therapies for Alzheimer’s disease, yet their biology remains unclear. Here we show, through multi-omic profiling of peripheral blood from three ARIA+ patients and matched controls, that ARIA is associated with coordinated reprogramming of CD8 + T cells. CD8+ effector memory (TEM) and terminally differentiated (TEMRA) subsets were expanded, clonally enriched, and transcriptionally primed for cytotoxicity and vascular trafficking. Transcription factor inference and metabolomics converged on glycolytic reprogramming favoring short-lived effector function. Ligand-receptor modeling revealed enhanced monocyte-to-T cell signaling through antigen presentation, adhesion, and chemokine axes, while integration with a …

From Fog To Function: An Occupational Therapist's Guide To Evaluating And Treating Cancer-Related Cognitive Impairments, Lauren E. Toner

Entry-Level Occupational Therapy Doctorate - Doctoral Capstone Symposium

Cancer – related cognitive impairment (CRCI) is a common side effect of cancer treatment that interferes with cancer survivors’ occupational performance, independence, and quality of life. Despite its high prevalence, CRCI remains under recognized and inconsistently addressed within oncology care. About 70% of individuals diagnosed with cancer report cognitive changes during or after treatment, yet many do not receive treatment. Occupational therapists are clinically trained to evaluate and treat functional cognition, activities of daily activities, instrumental activities of daily living, and client centered goals, positioning them as key providers in addressing CRCI. However, limited occupational therapy specific resources have hindered …

Nicotine Self-Administration And The Impacts On Medial Habenula And Interpeduncular Nucleus Neurophysiology, Nathan Alexander Olszewski

Theses, Dissertations and Capstones

Nicotine use is a tremendous public health issue in the United States, with over 23 million people being dependent on the substance. Low cessation rates associated with nicotine use are largely attributed to the withdrawal and craving symptoms that occur after abstinence of use from nicotine. The medial habenula (MHb) and interpeduncular nucleus (IPN) are two brain regions heavily associated and linked with nicotine withdrawal. Here, I sought to understand how these brain regions are altered in their physiology during nicotine intake. Utilizing E-Vape self-administration, mice were first taught to selfadminister nicotine of various, clinically relevant, dosages which correlate to …

Apoe4 Drives Maladaptive Heterogeneity And Immunometabolic Responses Of Astrocytes, Danielle S. Goulding, Holden C. Williams, Amy A. Gorman, Nicholas A. Devanney, Douglas A. Harrison, Adeline E. Walsh, Tony Tuck, Diana J. Zajac, Shannon L. Macauley, Steven Estus, Julia Tcw, Lance A. Johnson, Josh M. Morganti

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E4 (APOE4) is the strongest risk allele associated with the development of late onset Alzheimer’s disease (AD). Across the CNS, astrocytes are the predominant expressor of APOE while also being critical mediators of neuroinflammation and cerebral metabolism. APOE4 has been consistently linked with dysfunctional inflammation and metabolic processes, yet insights into the molecular constituents driving these responses remain unclear. Utilizing complementary approaches across humanized APOE mice and isogenic human iPSC astrocytes, we demonstrate that ApoE4 alters the astrocyte immunometabolic response to pro-inflammatory stimuli. Our findings show that ApoE4-expressing astrocytes acquire distinct transcriptional repertoires at single-cell and spatially-resolved domains, which …

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E. Irmen, Nicholas J. Constantino, Chanung Wang, Michael F. Kanan, Marco Colonna, Shannon L. Macauley, Jocelyn Y. Cheng, Ken Hatanaka, Margaret Moline, Erik S. Musiek

Sanders-Brown Center on Aging Faculty Publications

Background: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer’s disease (AD). The orexin/hypocretin system regulates sleep–wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

Methods: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …

Age-Related Ultrastructural Differences In The Dorsal Cortex Of The Inferior Colliculus In The Fischer Brown Norway Rat, Kylee M. Tenney, Dakota Smallridge, Gillian Barach, Gurveer Singh, Erin Beskitt, Justine Busby, Syllissa Duncan, Alexa Wawrzyniak, Brenda Vega, Nick Tokar, Andrew Ohl, Jesse Young, Jeffrey Mellott

Williams Honors College, Honors Research Projects

The inferior colliculus is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC. The ICd is a non-lemniscal nucleus that is well …

35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano

Department of Pediatrics Faculty Publications

HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well …

Educational Attainment And Symptom Improvement In Treatment-Resistant Depression: A Longitudinal Cohort Analysis Across Treatment Modalities, Marjorie Harrison, Giselli Scaini Msc, Phd, Aspen Viamontes

Summer Research Program Abstracts

No abstract provided.

Neurodevelopmental Outcomes After Posthemorrhagic Hydrocephalus Of Prematurity, Mekal S. Mathew, Rene Leal, Caroline L. Hanan, David J. Sun, Hasan K. Mubarak, Amelie D. Perrier, William E. Johnson, Micolette R. Mardik, Trevor R. Alwell, Christian Amezquita Contreras, Chance E. Hatfield, Peter H. Yang

Summer Research Program Abstracts

No abstract provided.

The Role Of P2y1 And P2y2 Receptors In Human Neural Stem Cell Proliferation, Daria Sokolova

Honors Undergraduate Theses

Endogenous neural stem cells (NSCs) are located in specialized niches of the adult brain and play a vital role in both neurogenesis and neuronal repair. However, declines in NSC proliferation and metabolism associated with age and pathology make these cells less efficient at responding to neurodegenerative disease. Understanding signaling pathways that regulate NSC function is therefore essential for the understanding and development of treatments for these conditions. P2Y receptors are G-protein-coupled purinergic receptors that are activated by extracellular nucleotides and regulate cellular metabolism and proliferation. Among the eight known P2Y subtypes, P2Y1 and P2Y2 have been linked to neuronal signaling …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego

Biological Sciences Faculty Publications

Postsynaptic scaffolding protein SAP90/PSD95-associated protein 3 (SAPAP3) modulates cortico-striatal signalling and regulates the maintenance of synaptic structure. Notably, SAPAP3 defects have been reported in several human psychiatric disorders that share pathophysiological features with Huntington’s disease (HD), a neurodegenerative disorder characterized by the expression of mutant huntingtin (mHTT) and marked dysfunction of cortico-striatal synapses and mitochondria. However, the role of SAPAP3 in mitochondrial function and HD pathophysiology remains unexplored. SAPAP3 was extracted from striatal synaptoneurosomes and analyzed by SWATH-MS proteomics to identify potential interactors, revealing SAPAP3 association with several mitochondrial proteins, particularly Mic60. These data were further complemented with proximity ligation …

Family Mental Health – A Case Report, Vikrant Arora, Medha Kosireddy, Mathumitha Ananth, Kishor M. Manohar Rao

Digital Journal of Clinical Medicine

Psychiatric illness in India is estimated to be 15% as per National Mental Health Survey 2015-16.  Mental health challenges within families, especially depression, anxiety disorders that are not common and when unaddressed exert cascading effects on all members, disrupting emotional cohesion, relational functioning, and socioeconomic stability. There are few case reports on entire family presenting to psychiatry department.

With informed consent a city-based middle-class family of non-consanguineous origin, where the 40-year-old female, presented with intractable limb pains and health anxiety, she had multiple consultation in last few months and her 48-year-old husband also had with episodic pains, irritability and her …

Unraveling The Significance Of Fecal Microrna Profile In Alzheimer’S Disease, Kavisha Katuwawala, Prashant Bharadwaj, Ian Martins, B. G.D.N.K. De Silva, Vincent Ho, Asiri Dissanayake, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), a complex neurodegenerative disorder characterised by progressive cognitive decline, affects millions globally. With no current cure, treatment focuses on symptom management and slowing disease progression. Early identification is therefore crucial. Fecal microRNA (miRNA) analysis is emerging as a promising non-invasive diagnostic tool. Evidence suggests that miRNAs present in fecal samples may regulate gene expression linked to AD pathology, impacting cellular functions and disease progression. Dietary factors critically influence gut microbiota composition and diversity, affecting brain health via the gut brain axis. Macronutrients such as carbohydrates, proteins, and fats modulate miRNA expression and gut microbiota, influencing AD risk. …

Prevalence Of Dementia In Selected Middle East And North Africa (Mena) Countries: A Systematic Review And Meta-Analysis, Mohsen Sedighi, Mohammad Hasan Shahabi, Alireza Amanollahi, Khurshid Alam, Soudabeh Shemehsavar, Zahra Shirzadi, Serena Sabatini, Ahmad R. Khatoonabadi, Matthew Prina, Akram A. Hosseini, Claire V. Burley, Jennifer Dunne, Simin Mahinrad, Iman Dajani, Ralph N. Martins, Blossom C.M. Stephan, Ali Chaari, Hamid R. Sohrabi

Research outputs 2022 to 2026

Data on dementia epidemiology in the Middle East and North Africa (MENA) region is limited. This systematic review and meta-analysis examined dementia prevalence across MENA. Databases were searched up to October 2024. Analyses were stratified by country and sex. Pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI). Fifty-two studies on the selected countries met inclusion criteria, covering 87,219 individuals with dementia from a total population of 1,045,908. The pooled prevalence was 12.16% (95% CI: 9.61–14.96) for the region and the Israel had the highest prevalence (17.00%), followed by Iran (13.20%), Turkey (11.40%), Saudi Arabia …

Pain In People With Dementia Is A Significant Contributor To Increased Professional Caregiver Burden: Results Of An Observation Study, Kreshnik Hoti, Ipsit Vahia, Paola Chivers, Jeffery Hughes

Research outputs 2022 to 2026

Aim: To investigate the association between the presence of neuropsychological symptoms, professional caregiver burden and pain intensity.

Methods: Eleven neuropsychiatric symptoms reportedly associated with caregiver burden which are included within the PainChek® pain assessment tool were identified: aggressiveness, inappropriate behavior, distressed, verbally offensive, confusion, restlessness, pacing and wandering, crying, screaming, altered sleep and resisting care. A caregiver burden score based on binary scoring of the presence of these indicators was calculated (summative score range from 0 to 11). Generalized estimating equations were used to evaluate the relationships between (1) pain score and sum of caregiver indicators present and (2) pain …

Neural Correlates Of Cognitive Fatigue In Regular Cannabis Users And Non-Users: A Pilot Fnirs Study, Mariia Vistyzenko

Theses and Dissertations (Comprehensive)

Background: Cognitive fatigue impairs performance across multiple domains, yet how regular cannabis use affects fatigue responses remains unclear. This pilot study investigated neural and behavioural correlates of cognitive fatigue in abstinent cannabis users versus non-users.

Methods: Twenty-six participants (18 non-users, 8 regular cannabis users after 24-hour abstinence) completed cognitive tasks before and after a 60-minute Sustained Attention to Response Task (SART) designed to induce fatigue. Tasks assessed working memory (N-Back), cognitive flexibility (Wisconsin Card Sorting), psychomotor speed (Digit Symbol Substitution), sustained attention (Continuous Performance Task), inhibition (Stroop, Stop Signal), and motion perception. Functional near-infrared spectroscopy (fNIRS) continuously monitored prefrontal cortex …

Gut Microbial Composition And Short-Chain Fatty Acid Metabolism In Cognitively Unimpaired Adults Stratified By Amyloid-Β Status, D. M.Sithara Dissanayaka, Thilini N. Jayasinghe, Hamid R. Sohrabi, Stephanie R. Rainey-Smith, Kevin Taddei, Colin L. Masters, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Short-chain fatty acids (SCFAs) produced by gut microbial fermentation influence host metabolism and neuroinflammatory processes implicated in Alzheimer’s disease (AD). However, the relationship between fecal SCFAs, microbial taxa, and cerebral amyloid-β (Aβ) burden in cognitively unimpaired individuals remains unclear. Fecal SCFAs were quantified using GC-MS, and microbial species were profiled by shotgun metagenomics in 87 participants. Associations between SCFAs, demographics, APOE ε4 status, and Aβ burden were tested using nonparametric statistics and multivariable regression. Microbial–SCFA links were evaluated using Spearman correlations and multivariate ordinations, with mediation analysis exploring potential indirect pathways. Acetate was the predominant SCFA and demonstrated the most …

When Does Alzheimer's Disease Start? Plasma Aβ42/40 Assays Show Steep Changes At Aβ-Pet Centiloid 15, Mean Age Of 66 Years, Rodrigo Cánovas, Timothy Cox, Vincent Doré, Pierrick Bourgeat, Jurgen Fripp, Azadeh Feizpour, Rosita Shishegar, Christopher J. Fowler, Simon M. Laws, Tenielle Porter, Stephanie Rainey-Smith, Leslie M. Shaw, Randall J. Bateman, Yan Li, Ovod Vitaliy, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Akinori Nakamura, Takeshi Iwatsubo, Takeshi Ikeuchi, Takashi Kato, Paul Maruff, Hamid R. Sohrabi, Christopher C. Rowe, Ralph Martins, Colin L. Masters, James Doecke

Research outputs 2022 to 2026

Objective: Sporadic late-onset Alzheimer's disease (AD) is characterized by a long pre-clinical phase where amyloid-beta (Aβ) and tau begin to accumulate in the brain. The primary objective was to determine the age at which AD starts by finding the average population age when both positron emission tomography (PET) Aβ (Aβ-PET) and plasma Aβ42/40 become abnormal. Methods: Two high performance immunoprecipitation-mass spectrometry (IP-MS) assays (WashU/C2N and Shimadzu) were tested on samples from 1,450 participants who were diagnosed as cognitively unimpaired (CU), mild cognitive impairment (MCI), or AD-dementia across 4 international cohorts. Natural history modeling and trajectory analyses of the combined Aβ-PET …

Insulin Resistance As A Mediator Of Physical Activity's Effects On Beta-Amyloid Accumulation And Tau Phosphorylation: A Scoping Review, Michael G. Slee, Joanne Scotney, Stephanie R. Rainey-Smith, Kirk I. Erickson, Hamid R. Sohrabi, Giuseppe Verdile, Belinda M. Brown

Research outputs 2022 to 2026

Background Type 2 diabetes is associated with increased Alzheimer’s disease risk and brain beta amyloid (Aβ) burden, suggesting an underlying mechanistic relationship between Alzheimer’s disease and type 2 diabetes. Animal studies show exercise reduces levels of brain Aβ and tau, and while human studies are somewhat limited, some studies have reported physical activity is associated with lower brain Aβ and tau levels. Exercise has well established links to reductions in insulin resistance; thus, as physical activity can impact both insulin resistance and Alzheimer’s disease pathology and/or biomarkers, it is reasonable to hypothesise that a mediating relationship may exist. The objective …

Plasma Aβ42/40 Predicts Progression From Aβ-Amyloid Negative To Positive Pet Scans, Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D. Doecke, Rodrigo Canovas, Simon M. Laws, Tenielle Porter, Kun Huang, Christopher Fowler, Ralph N. Martins, Paul Maruff, Hamid R. Sohrabi, Michael W. Weiner, John C. Morris, Tammie L.S. Benzinger, Suzanne E. Schindler, Randall J. Bateman, Yan Li, Ovod Vitaliy, Larry Ward, Jurgen Mejan-Fripp, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Background The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether this reflects Aβ changes in plasma before PET-detectable. Objectives To assess the influence of Aβ42/40 positivity on risk of progression to Aβ PET positivity, and feasibility of using plasma Aβ42/40 tests to enrich a primary prevention trial. Design A prospective longitudinal cohort study. Setting Participants of Australian Imaging, Biomarkers and Lifestyle study (AIBL), Alzheimer’s Disease Neuroimaging Initiative (ADNI), and Open Access Series of Imaging Studies 3 (OASIS3). …

The Associations Between Sleep Environment Factors And Sleep Health In Individuals Living With Neurological Conditions, Mitchell Turner, Laws, Madeline Griffiths, Travis Cruickshank

Research outputs 2022 to 2026

Objectives: To explore associations between air temperature and light in the sleeping environment and sleep health in individuals with neurological conditions. Methods: The sleep health of 46 individuals with neurological conditions (mean age 51.37 ± 14.24 years; 20 males, 26 females) was measured using the Sleep Health Index (SHI). Air temperature and light data were captured across seven days using a light/temperature data logger positioned next to the participant’s bed. Data recorded during the participants’ sleeping periods (determined using a sleep diary) were analyzed. Linear regression models were used to assess the associations between air temperature and light and sleep …