Medical Sciences Commons^™

Complete Genome Sequences Of Toxigenic Clostridioides Difficile Isolated From Australian Feral Horses, Natasza Hain-Saunders, Daniel R. Knight, Mieghan Bruce, Thomas V. Riley

Research outputs 2022 to 2026

Recent increases in community-associated Clostridioides difficile infections have highlighted the importance of monitoring toxigenic C. difficile from animal and environmental sources. We provide the complete circularized genomes of two toxigenic C. difficile strains isolated from feral horse faeces. Genome N64 (sequence type 964) consists of a single chromosome of 4,078,791 bp, while genome H251 (sequence type 963) comprises one chromosome (4,304,722 bp) and three plasmids (150,942 bp, 11,534 bp, and 9,074 bp).

Genome-Wide Cross-Disease Analyses Highlight Causality And Shared Biological Pathways Of Type 2 Diabetes With Gastrointestinal Disorders, Emmanuel O. Adewuyi, Tenielle Porter, Eleanor K. O’Brien, Oladapo Olaniru, Giuseppe Verdile, Simon M. Laws

Research outputs 2022 to 2026

Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and …

Pain Prevalence, Intensity, And Association With Neuropsychiatric Symptoms Of Dementia In Immigrant And Non-Immigrant Aged Care Residents In Australia, Pelden Chejor, Mustafa Atee, Patricia Cain, Daniel Whiting, Thomas Morris, Davina Porock

Research outputs 2022 to 2026

Pain recognition for culturally diverse people is complex as pain experience is subjective and influenced by cultural background. We compared the prevalence, intensity, and association of pain with neuropsychiatric symptoms (NPS) between immigrants and non-immigrants living with dementia in residential aged care homes (RACHs) who were referred to two Dementia Support Australia programs. Immigrant status was defined by the documented country of birth. Pain and NPS were assessed using PainChek® and the Neuropsychiatric Inventory, respectively. Subgroup analyses were also completed for English-speaking and non-English-speaking immigrants. A total of 17,637 referrals [immigrants, n = 6340; non-immigrants, n = 11,297] from 2792 …

Clearance And Transport Of Amyloid Β By Peripheral Monocytes Correlate With Alzheimer’S Disease Progression, Xin Huang, Chris Fowler, Yihan Li, Qiao Xin Li, Jiaqi Sun, Yijun Pan, Liang Jin, Keyla A. Perez, Céline Dubois, Yen Y. Lim, Candace Drysdale, Rebecca L. Rumble, Holly R. Chinnery, Christopher C. Rowe, Ralph N. Martins, Paul Maruff, James D. Doecke, Yong Lin, Abdel A. Belaidi, Kevin J. Barnham, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and …

Potentially Causal Association Between Immunoglobulin G N-Glycans And Cardiometabolic Diseases: Bidirectional Two-Sample Mendelian Randomization Study, Xiaoni Meng, Di Liu, Meiling Cao, Wei Wang, Youxin Wang

Research outputs 2022 to 2026

Background: Observational studies support that altered immunoglobulin G (IgG) N-glycosylation and inflammatory factors are associated with cardiometabolic diseases (CMDs); nevertheless, the causality between them remains unclear. Methods: Two-sample Mendelian randomization (MR) analyses were conducted to systematically investigate the bidirectional causality between IgG N-glycans and nine CMDs in both East Asians and Europeans. Results: In the forward MR analysis, the univariable MR analysis presented suggestive causality of 14 and eight genetically instrumented IgG N-glycans with CMDs in East Asians and Europeans, respectively; the multivariable MR analysis showed that ten and 11 pairs of glycan-CMD associations were identified in East Asian and …

Detection And Staging Of Alzheimer's Disease By Plasma Ptau217 On A High Throughput Immunoassay Platform, Azadeh Feizpour, James David Doecke, Vincent Doré, Natasha Krishnadas, Kun Huang, Pierrick Bourgeat, Simon Matthew Laws, Christopher Fowler, Joanne Robertson, Lucy Mackintosh, Scott Ayton, Ralph Martins, Stephanie Ruth Rainey-Smith, Kevin Taddei, Larry Ward, Eddie Stage, Anthony Wilson Bannon, Colin Louis Masters, Jurgen Fripp, Victor Luis Villemagne, Christopher Cleon Rowe

Research outputs 2022 to 2026

Background: Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Methods: Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Findings: …

Persistent Inward Currents In Tibialis Anterior Motoneurons Can Be Reliably Estimated Within The Same Session, Thomas Lapole, Ricardo N.O. Mesquita, Stéphane Baudry, Robin Souron, Eleanor K. O'Brien, Callum G. Brownstein, Vianney Rozand

Research outputs 2022 to 2026

The response of spinal motoneurons to synaptic input greatly depends on the activation of persistent inward currents (PICs), the contribution of which can be estimated through the paired motor unit technique. Yet, the intra-session test–retest reliability of this measurement remains to be fully established. Twenty males performed isometric triangular dorsiflexion contractions to 20 and 50 % of maximal torque at baseline and after a 15-min resting period. High-density electromyographic signals (HD-EMG) of the tibialis anterior were recorded with a 64-electrode matrix. HD-EMG signals were decomposed, and motor units tracked across time points to estimate the contribution of PICs to motoneuron …

Anti-Inflammatory And Anti-(Lymph)Angiogenic Properties Of An Abcb5+ Limbal Mesenchymal Stem Cell Population, Berbang Meshko, Thomas L. A. Volatier, Johanna Mann, Mark A. Kluth, Christoph Ganss, Markus H. Frank, Natasha Y. Frank, Bruce R. Ksander, Claus Cursiefen, Maria Notara

Research outputs 2022 to 2026

Corneal transparency and avascularity are essential for vision. The avascular cornea transitions into the vascularized conjunctiva at the limbus. Here, we explore a limbal stromal cell sub-population that expresses ABCB5 and has mesenchymal stem cell characteristics. Human primary corneal stromal cells were enriched for ABCB5 by using FACS sorting. ABCB5+ cells expressed the MSC markers CD90, CD73, and CD105. ABCB5+ but not ABCB5− cells from the same donor displayed evidence of pluripotency with a significantly higher colony-forming efficiency and the ability of trilineage differentiation (osteogenic, adipogenic, and chondrogenic). The ABCB5+ cell secretome demonstrated lower levels of the pro-inflammatory protein MIF …

Investigating Genetic Overlap Between Alzheimer’S Disease, Lipids, And Coronary Artery Disease: A Large-Scale Genome-Wide Cross Trait Analysis, Artika Kirby, Tenielle Porter, Emmanuel O. Adewuyi, Simon M. Laws

Research outputs 2022 to 2026

There is evidence to support a link between abnormal lipid metabolism and Alzheimer’s disease (AD) risk. Similarly, observational studies suggest a comorbid relationship between AD and coronary artery disease (CAD). However, the intricate biological mechanisms of AD are poorly understood, and its relationship with lipids and CAD traits remains unresolved. Conflicting evidence further underscores the ongoing investigation into this research area. Here, we systematically assess the cross-trait genetic overlap of AD with 13 representative lipids (from eight classes) and seven CAD traits, leveraging robust analytical methods, well-powered large-scale genetic data, and rigorous replication testing. Our main analysis demonstrates a significant …

Apolipoprotein Ε4 Is Associated With Increased Risk Of Fall- And Fracture-Related Hospitalization: The Perth Longitudinal Study Of Ageing Women, Jedd Pratt, Jack Dalla Via, Craig Sale, Abadi K. Gebre, Blossom C.M. Stephan, Simon Laws, Kun Zhu, Wai H. Lim, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Apolipoprotein ε4 (APOE ε4) may be a genetic risk factor for reduced bone mineral density (BMD) and muscle function, which could have implications for fall and fracture risk. We examined the association between APOE ε4 status and long-term fall- and fracture-related hospitalization risk in older women. A total of 1 276 community-dwelling women from the Perth Longitudinal Study of Aging Women (mean age ± SD = 75.2 ± 2.7 years) were included. At baseline, women underwent APOE genotyping and detailed phenotyping for covariates including prevalent falls and fractures, as well as health and lifestyle factors. The association between APOE ε4 …

Resting State Electrophysiological Profiles And Their Relationship With Cognitive Performance In Cognitively Unimpaired Older Adults: A Systematic Review, Brenda Chino, David López-Sanz, Sandra Doval, Lucía Torres-Simón, Jaisalmer De Frutos Lucas, Lydia Giménez-Llort, Jonathan Zegarra-Valdivia, Fernando Maestú

Research outputs 2022 to 2026

Background: Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration. Objective: In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life. Methods: With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. After applying inclusion and …

The Relationship Between Diet, Depression, And Alzheimer's Disease: A Narrative Review, Hilal Salim Said Al Shamsi, Stephanie R. Rainey-Smith, Samantha L. Gardener, Hamid R. Sohrabi, Rodrigo Canovas, Ralph N. Martins, Warnakulasuriya Mary Ann Dipika Binosha Fernando

Research outputs 2022 to 2026

Purpose of Review: This narrative review evaluates the role of diet in the relationship between depression and Alzheimer's disease (AD). Recent Findings: AD and depression are often comorbid, and depression appears to independently increase the future risk of AD. Evidence suggests diet influences the risk of both conditions directly and indirectly. Diet impacts neurochemical and biological processes that may affect the development and progression of depression and cognitive dysfunction. The dietary components offering the greatest protection against depression and AD are yet to be determined. Current evidence highlights the importance of polyphenolic compounds, folate, B vitamins, and polyunsaturated fatty acids, …

The Crosstalk Between Amyloid-Β, Retina, And Sleep For The Early Diagnosis Of Alzheimer's Disease: A Narrative Review, Isaiah Lorenzo De Guia, Shaun Eslick, Sharon L. Naismith, Swathi Kanduri, Tejal M. Shah, Ralph N. Martins

Research outputs 2022 to 2026

Alzheimer's disease (AD) is the most common type of dementia, which is characterised by progressive memory loss and accumulation of hallmark markers amyloid-β (Aβ) and neurofibrillary tangles in the diseased brain. The current gold standard diagnostic methods have limitations of being invasive, costly, and not easily accessible. Thus, there is a need for new avenues, such as imaging the retina for early AD diagnosis. Sleep disruption is symptomatically frequent across preclinical and AD subjects. As circadian activity, such as the sleep-wake cycle, is linked to the retina, analysis of their association may be useful additions for achieving predictive AD diagnosis. …

Association Of Basal Forebrain Atrophy With Cognitive Decline In Early Alzheimer Disease, Ying Xia, Vincent Dore, Jurgen Fripp, Pierrick Bourgeat, Simon M. Laws, Christopher J. Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Christopher Rowe, Colin L. Masters, Elizabeth J. Coulson, Paul Maruff

Research outputs 2022 to 2026

Background and Objectives: In early Alzheimer disease (AD), β-amyloid (Aβ) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD.

Methods: Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aβ-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aβ status, yielding groups …

Non-Invasive Brain Stimulation As Treatment For Motor Impairment In People With Parkinson's Disease: Protocol For An Umbrella Review, Dale M. Harris, Steven J. O'Bryan, Christopher Latella

Research outputs 2022 to 2026

Background Parkinson's disease (PD) is a progressive neurodegenerative disorder that predominantly affects movement and currently has no cure. Alongside medication, non-invasive brain stimulation (NIBS) may be used as an adjunct therapy to attenuate the motor symptoms experienced by people with PD. However, there is considerable heterogeneity in the evidence exploring the effects of NIBS for improving aspects of physical function in people with PD. Therefore, this protocol paper will outline the objectives, structure and procedure of a proposed umbrella review which will comprehensively summarise and map the current body evidence on the effectiveness of NIBS for improving physical function in …

Prevention Of Dementia Using Mobile Phone Applications (Prodemos): A Multinational, Randomised, Controlled Effectiveness–Implementation Trial, Eric P.Moll Van Charante, Marieke P. Hoevenaar-Blom, Manshu Song, Sandrine Andrieu, Linda Barnes, Cindy Birck, Rachael Brooks, Nicola Coley, Esmé Eggink, Jean Georges, Melanie Hafdi, Willem A. Van Gool, Ron Handels, Haifeng Hou, Jihui Lyu, Yixuan Niu, Libin Song, Wenzhi Wang, Youxin Wang, Anders Wimo, Yueyi Yu, Jinxia Zhang, Wei Zhang, Carol Brayne, Wei Wang, Edo Richard

Research outputs 2022 to 2026

Background: The expected increase of dementia prevalence in the coming decades will mainly be in low-income and middle-income countries and in people with low socioeconomic status in high-income countries. This study aims to reduce dementia risk factors in underserved populations at high-risk using a coach-supported mobile health (mHealth) intervention. Methods: This open-label, blinded endpoint, hybrid effectiveness–implementation randomised controlled trial (RCT) investigated whether a coach-supported mHealth intervention can reduce dementia risk in people aged 55–75 years of low socioeconomic status in the UK or from the general population in China with at least two dementia risk factors. The primary effectiveness outcome …

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

Research outputs 2022 to 2026

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

Bidirectional Two-Sample Mendelian Randomization Study Of Immunoglobulin G N-Glycosylation And Senescence-Associated Secretory Phenotype, Haotian Wang, Di Liu, Xiaoni Meng, Wenxin Sun, Cancan Li, Huimin Lu, Deqiang Zheng, Lijuan Wu, Shengzhi Sun, Youxin Wang

Research outputs 2022 to 2026

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189–0.969) and GP17 (OR = 0.709, 95%CI = …

Cognitive And Neuroscientific Perspectives Of Healthy Ageing, Jon B. Prince, Helen L. Davis, Jane Tan, Katrina Muller-Townsend, Shaun Markovic, David M. G. Lewis, Brianne Hastie, Matthew B. Thompson, Peter D. Drummond, Hakuei Fujiyama, Hamid R. Sohrabi

Research outputs 2022 to 2026

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021–2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, …

Methylgenotyper: Accurate Estimation Of Snp Genotypes And Genetic Relatedness From Dna Methylation Data, Yi Jiang, Minghan Qu, Minghui Jiang, Xuan Jiang, Shane Fernandez, Tenielle Porter, Simon M. Laws, Colin L. Masters, Huan Guo, Shanshan Cheng, Chaolong Wang

Research outputs 2022 to 2026

Epigenome-wide association studies (EWAS) are susceptible to widespread confounding caused by population structure and genetic relatedness. Nevertheless, kinship estimation is challenging in EWAS without genotyping data. Here, we proposed MethylGenotyper, a method that for the first time enables accurate genotyping at thousands of single nucleotide polymorphisms (SNPs) directly from commercial DNA methylation microarrays. We modeled the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimated parameters with an expectation-maximization algorithm. We conducted extensive simulations to demonstrate the performance of the method. When applying MethylGenotyper to the Infinium EPIC array data …

Intensity-Dependent Effects Of Tdcs On Motor Learning Are Related To Dopamine, Li Ann Leow, Jiaqin Jiang, Samantha Bowers, Yuhan Zhang, Paul E. Dux, Hannah L. Filmer

Research outputs 2022 to 2026

Non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are popular methods for inducing neuroplastic changes to alter cognition and behaviour. One challenge for the field is to optimise stimulation protocols to maximise benefits. For this to happen, we need a better understanding of how stimulation modulates cortical functioning/behaviour. To date, there is increasing evidence for a dose-response relationship between tDCS and brain excitability, however how this relates to behaviour is not well understood. Even less is known about the neurochemical mechanisms which may drive the dose-response relationship between stimulation intensities and behaviour. Here, we examine the effect …

Healing Right Way Randomised Control Trial Enhancing Rehabilitation Services For Aboriginal People With Brain Injury In Western Australia: Translation Principles And Activities, Neil Drew, Meaghan Mcallister, Juli Coffin, Melanie Robinson, Judith Katzenellenbogen, Elizabeth Armstrong

Research outputs 2022 to 2026

Background: This report provides the theory, method and practice of culturally secure translation and knowledge exchange in the Healing Right Way Clinical Trial (2017–2022), outlining activities to date. Healing Right Way was a stepped wedge cluster randomised controlled trial conducted in Western Australia, aimed at enhancing rehabilitation services and quality of life for Aboriginal Australians following acquired brain injury. The trial translation plan was aspirational and action-oriented, with its implementation iterative and ongoing. Translational activities aimed to inform service and research planning for Aboriginal people with brain injury. Situated in the intercultural space, the work guards against undertaking activities that …

Suboptimal Self-Reported Sleep Efficiency And Duration Are Associated With Faster Accumulation Of Brain Amyloid Beta In Cognitively Unimpaired Older Adults, Louise N. Pivac, Belinda M. Brown, Kelsey R. Sewell, James D. Doecke, Victor L. Villemagne, Vincent Doré, Michael Weinborn, Hamid R. Sohrabi, Samantha L. Gardener, Romola S. Bucks, Simon M. Laws, Kevin Taddei, Paul Maruff, Colin L. Masters, Christopher Rowe, Ralph N. Martins, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

Introduction: This study investigated whether self-reported sleep quality is associated with brain amyloid beta (AB) accumulation. METHODS: Linear mixed effect model analyses were conducted for 189 cognitively unimpaired (CU) older adults (mean ± standard deviation 74.0 ± 6.2; 53.2% female), with baseline self-reported sleep data, and positron emission tomography-determined brain AB measured over a minimum of three time points (range 33.3–72.7 months). Analyses included random slopes and intercepts, interaction for apolipoprotein E (APOE) 4 allele status, and time, adjusting for sex and baseline age.

Results: Sleep duration < 6 hours, in APOE 4 carriers, and sleep efficiency < 65%, in the whole sample and APOE 4 non-carriers, is associated with faster accumulation of brain AB. DISCUSSION: These findings suggest a role for self-reported suboptimal sleep efficiency and duration in the accumulation of Alzheimer's disease (AD) neuropathology in CU individuals. Additionally, poor sleep efficiency represents a potential route via which individuals at lower genetic risk may progress to preclinical AD. Highlights: In cognitively unimpaired older adults self-report sleep is associated with brain amyloid beta (AB) accumulation. Across sleep characteristics, this relationship differs by apolipoprotein E (APOE) genotype. Sleep duration < 6 hours is associated with faster brain AB accumulation in APOE 4 carriers. Sleep efficiency < 65% is associated with faster brain AB accumulation in APOE 4 non-carriers. Personalized sleep interventions should be studied for potential to slow AB accumulation.

The Australian Multidomain Approach To Reduce Dementia Risk By Protecting Brain Health With Lifestyle Intervention Study (Au-Arrow): A Study Protocol For A Single-Blind, Multi-Site, Randomized Controlled Trial, Samantha L. Gardener, Stephanie J. Fuller, Sharon L. Naismith, Laura Baker, Miia Kivipelto, Victor L. Villemagne, Stuart M. Grieve, Paul Yates, Stephanie R. Rainey-Smith, Juliana Chen, Belinda Thompson, Nicola J. Armstrong, Malika G. Fernando, Carolina B. Castro, Silochna Meghwar, Rema Raman, Andrew Gleason, Catriona Ireland, Roger Clarnette, Kaarin J. Anstey, Kevin Taddei, Manohar Garg, Hamid R. Sohrabi, Ralph N. Martins

Research outputs 2022 to 2026

Introduction: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER.

Method: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55–79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a …

Investigating The Genetic Makeup Of The Major Histocompatibility Complex (Mhc) In The United Arab Emirates Population Through Next-Generation Sequencing, Nour A. D. Marzouka, Halima Alnaqbi, Amira Al-Aamri, Guan Tay, Habiba Alsafar

Research outputs 2022 to 2026

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the …

The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis …

The Association Between Plasma Igg N-Glycosylation And Neonatal Hypoxic–Ischemic Encephalopathy: A Case-Control Study, Liangao Wang, Xinxia Lu, Meng Wang, Xuezhen Zhao, Peirui Li, Haitao Zhang, Qingtang Meng, Yujing Zhang, Yingjie Wang, Wei Wang, Long Ji, Haifeng Hou, Dong Li

Research outputs 2022 to 2026

Introduction: Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. Methods: This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used …

Longitudinal Associations Between Exercise And Biomarkers In Autosomal Dominant Alzheimer's Disease, Kelsey R. Sewell, James D. Doecke, Chengjie Xiong, Tammie Benzinger, Colin L. Masters, Christoph Laske, Mathias Jucker, Francisco Lopera, Brian A. Gordon, Jorge Llibre-Guerra, Johannes Levin, Edward D. Huey, Jason Hassenstab, Peter R. Schofield, Gregory S. Day, Nick C. Fox, Jasmeer Chhatwal, Laura Ibanez, Jee Hoon Roh, Richard Perrin, Jae Hong Lee, Ralph N. Martins, Stephanie Rainey-Smith, Samantha L. Gardener, Hamid R. Sohrabi, Belinda Brown

Research outputs 2022 to 2026

INTRODUCTION: We investigated longitudinal associations between self-reported exercise and Alzheimer's disease (AD)-related biomarkers in individuals with autosomal dominant AD (ADAD) mutations. METHODS: Participants were 308 ADAD mutation carriers aged 39.7 ± 10.8 years from the Dominantly Inherited Alzheimer's Network. Weekly exercise volume was measured via questionnaire and associations with brain volume (magnetic resonance imaging), cerebrospinal fluid biomarkers, and brain amyloid beta (Aβ) measured by positron emission tomography were investigated. RESULTS: Greater volume of weekly exercise at baseline was associated with slower accumulation of brain Aβ at preclinical disease stages β = –0.16 [–0.23 to –0.08], and a slower decline in …

Variations In The Germinal Center Response Revealed By Genetically Diverse Mouse Strains, Anne Marie Aubin, Daria Vdovenko, Roxanne Collin, Lois Balmer, Lise Coderre, Grant Morahan, Félix Lombard-Vadnais, Sylvie Lesage

Research outputs 2022 to 2026

The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we …

Sleep Discrepancy And Brain Glucose Metabolism In Community-Dwelling Older Adults, Nadia Soh, Michael Weinborn, James D. Doecke, Rodrigo Canovas, Vincent Doré, Ying Xia, Jurgen Fripp, Kevin Taddei, Romola S. Bucks, Hamid R. Sohrabi, Ralph N. Martins, Melissa Ree, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

Sleep discrepancy (negative discrepancy reflects worse self-reported sleep than objective measures, such as actigraphy, and positive discrepancy the opposite) has been linked to adverse health outcomes. This study is first to investigate the relationship between sleep discrepancy and brain glucose metabolism (assessed globally and regionally via positron emission tomography), and to evaluate the contribution of insomnia severity and depressive symptoms to any associations. Using data from cognitively unimpaired community-dwelling older adults (N = 68), cluster analysis was used to characterise sleep discrepancy (for total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)), and logistic regression was …