Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 14 of 14
Full-Text Articles in Medicine and Health Sciences
Relationship Of Cognition And Alzheimer’S Disease With Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap And Mendelian Randomisation Analysis, Emmanuel O. Adewuyi, Eleanor K. O’Brien, Tenielle Porter, Simon M. Laws
Relationship Of Cognition And Alzheimer’S Disease With Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap And Mendelian Randomisation Analysis, Emmanuel O. Adewuyi, Eleanor K. O’Brien, Tenielle Porter, Simon M. Laws
Research outputs 2022 to 2026
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders — peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10 − 5) bivariate local genetic …
Assessment Of A Polygenic Hazard Score For The Onset Of Pre-Clinical Alzheimer’S Disease, Michael Vacher, Vincent Doré, Tenielle Porter, Lidija Milicic, Victor L. Villemagne, Pierrick Bourgeat, Sam C. Burnham, Timothy Cox, Colin L. Masters, Christopher C. Rowe, Jurgen Fripp, James D. Doecke, Simon M. Laws
Assessment Of A Polygenic Hazard Score For The Onset Of Pre-Clinical Alzheimer’S Disease, Michael Vacher, Vincent Doré, Tenielle Porter, Lidija Milicic, Victor L. Villemagne, Pierrick Bourgeat, Sam C. Burnham, Timothy Cox, Colin L. Masters, Christopher C. Rowe, Jurgen Fripp, James D. Doecke, Simon M. Laws
Research outputs 2022 to 2026
Background: With a growing number of loci associated with late-onset (sporadic) Alzheimer’s disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD. In this study, we assessed the predictive power and transferability of this PHS in an independent cohort, to support its clinical utility. Results: Using genotype and imaging data from 780 individuals enrolled in …
Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile
Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile
Research outputs 2022 to 2026
Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of …
Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria
Efficacy And Safety Of A Brain-Penetrant Biologic Tnf-Α Inhibitor In Aged App/Ps1 Mice, Weijun Ou, Yuu Ohno, Joshua Yang, Devaraj V. Chandrashekar, Tamara Abdullah, Jiahong Sun, Riley Murphy, Chuli Roules, Nataraj Jagadeesan, David H. Cribbs, Rachita K. Sumbria
Pharmacy Faculty Articles and Research
Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating …
Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han
Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han
Pharmacy Faculty Articles and Research
Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …
Sleep, Sirtuin 1 And Alzheimer’S Disease: A Review, Mehrane Mehramiz, Tenielle Porter, Simon Laws, Stephanie R. Rainey-Smith
Sleep, Sirtuin 1 And Alzheimer’S Disease: A Review, Mehrane Mehramiz, Tenielle Porter, Simon Laws, Stephanie R. Rainey-Smith
Research outputs 2022 to 2026
Sleep plays a major role in brain health, and cognition. Disrupted sleep is a well-described symptom of Alzheimer’s disease (AD). However, accumulating evidence suggests suboptimal sleep also increases AD risk. The deacetylase Sirtuin 1 (Sirt 1), encoded by the SIRT1 gene, impacts sleep via its relationship to wake-sleep neurotransmitters and somnogens. Evidence from animal and human studies supports a significant and complex relationship between sleep, Sirt 1/ SIRT1 and AD. Numerous hypotheses attempt to explain the critical impact of Sirt 1/ SIRT1 on wake- and sleep- promoting neurons, their related mechanisms and neurotransmitters. However, there is a paucity of studies …
Visually Identified Tau 18f-Mk6240 Pet Patterns In Symptomatic Alzheimer's Disease, Natasha Krishnadas, Kun Huang, Stephanie A. Schultz, Vincent Doré, Pierrick Bourgeat, Anita M. Y. Goh, Fiona Lamb, Svetlana Bozinovski, Samantha C. Burnham, Joanne S. Robertson, Simon M. Laws, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe
Visually Identified Tau 18f-Mk6240 Pet Patterns In Symptomatic Alzheimer's Disease, Natasha Krishnadas, Kun Huang, Stephanie A. Schultz, Vincent Doré, Pierrick Bourgeat, Anita M. Y. Goh, Fiona Lamb, Svetlana Bozinovski, Samantha C. Burnham, Joanne S. Robertson, Simon M. Laws, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe
Research outputs 2022 to 2026
Background: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice. Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles. Methods : Tau 18F-MK6240 PET images of 151 amyloid-β positive participants with mild cognitive impairment (MCI) and dementia were visually rated as: tau negative, limbic predominant (LP), …
Microrna, The Innate-Immune System And Sars-Cov-2, James M. Hill, Walter J. Lukiw
Microrna, The Innate-Immune System And Sars-Cov-2, James M. Hill, Walter J. Lukiw
School of Medicine Faculty Publications
The single-stranded viral RNA (ssvRNA) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 can be effectively inactivated by a number of natural ribonucleic acid-based host cell defenses. One of the most important of these defenses includes the actions of a class of small non-coding RNAs (sncRNAs) known as microRNAs (miRNAs). Via base-pair complementarity miRNAs are capable of specifically targeting ssvRNA sequences such as SARS-CoV-2 promoting its inactivation and neutralization. RNA-sequencing and bioinformatics analysis indicate that multiple naturally-occurring human miRNAs have extensive complementarity to the SARS-CoV-2 ssvRNA genome. Since miRNA abundance, speciation, and complexity vary significantly …
Sex Differences In The Association Between Cardiovascular Diseases And Dementia Subtypes: A Prospective Analysis Of 464,616 Uk Biobank Participants, Caiyun Dong, Chunmiao Zhou, Chunying Fu, Wenting Hao, Akihiko Ozaki, Nipun Shrestha, Salim S. Virani, Shiva Raj Mishra, Dongshan Zhu
Sex Differences In The Association Between Cardiovascular Diseases And Dementia Subtypes: A Prospective Analysis Of 464,616 Uk Biobank Participants, Caiyun Dong, Chunmiao Zhou, Chunying Fu, Wenting Hao, Akihiko Ozaki, Nipun Shrestha, Salim S. Virani, Shiva Raj Mishra, Dongshan Zhu
Office of the Provost
Background: Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown.
Methods: We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), …
Characterization Of Retinal Drusen In Subjects At High Genetic Risk Of Developing Sporadic Alzheimer’S Disease: An Exploratory Analysis, Inés López-Cuenca, Elena Salobrar-García, Inés Gil-Salgado, Lidia Sánchez-Puebla, Lorena Elvira-Hurtado, José A. Fernández-Albarral, Federico Ramírez-Toraño, Ana Barabash, Jaisalmer De Frutos-Lucas, Juan J. Salazar, José M. Ramírez, Ana I. Ramírez, Rosa De Hoz
Characterization Of Retinal Drusen In Subjects At High Genetic Risk Of Developing Sporadic Alzheimer’S Disease: An Exploratory Analysis, Inés López-Cuenca, Elena Salobrar-García, Inés Gil-Salgado, Lidia Sánchez-Puebla, Lorena Elvira-Hurtado, José A. Fernández-Albarral, Federico Ramírez-Toraño, Ana Barabash, Jaisalmer De Frutos-Lucas, Juan J. Salazar, José M. Ramírez, Ana I. Ramírez, Rosa De Hoz
Research outputs 2022 to 2026
Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ε4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH-or FH+) and …
Comprehensive Analysis Of Epigenetic Clocks Reveals Associations Between Disproportionate Biological Ageing And Hippocampal Volume, Lidija Milicic, Michael Vacher, Tenielle Porter, Vincent Doré, Samantha C. Burnham, Pierrick Bourgeat, Rosita Shishegar, James Doecke, Nicola J. Armstrong, Rick Tankard, Paul Maruff, Colin L. Masters, Christopher C. Rowe, Victor L. Villemagne, Simon M. Laws, Alzheimer’S Disease Neuroimaging Initiative, Australian Imaging Biomarkers And Lifestyle (Aibl) Study
Comprehensive Analysis Of Epigenetic Clocks Reveals Associations Between Disproportionate Biological Ageing And Hippocampal Volume, Lidija Milicic, Michael Vacher, Tenielle Porter, Vincent Doré, Samantha C. Burnham, Pierrick Bourgeat, Rosita Shishegar, James Doecke, Nicola J. Armstrong, Rick Tankard, Paul Maruff, Colin L. Masters, Christopher C. Rowe, Victor L. Villemagne, Simon M. Laws, Alzheimer’S Disease Neuroimaging Initiative, Australian Imaging Biomarkers And Lifestyle (Aibl) Study
Research outputs 2022 to 2026
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant …
Mitoprotective Effects Of A Synergistic Nutraceutical Combination: Basis For A Prevention Strategy Against Alzheimer’S Disease, Dona P.W. Jayatunga, Eugene Hone, Binosha W.M.A. Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins
Mitoprotective Effects Of A Synergistic Nutraceutical Combination: Basis For A Prevention Strategy Against Alzheimer’S Disease, Dona P.W. Jayatunga, Eugene Hone, Binosha W.M.A. Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins
Research outputs 2022 to 2026
Evidence to date suggests the consumption of food rich in bioactive compounds, such as polyphenols, flavonoids, omega-3 fatty acids may potentially minimize age-related cognitive decline. For neurodegenerative diseases, such as Alzheimer’s disease (AD), which do not yet have definitive treatments, the focus has shifted toward using alternative approaches, including prevention strategies rather than disease reversal. In this aspect, certain nutraceuticals have become promising compounds due to their neuroprotective properties. Moreover, the multifaceted AD pathophysiology encourages the use of multiple bioactive components that may be synergistic in their protective roles when combined. The objective of the present study was to determine …
A Synergistic Combination Of Dha, Luteolin, And Urolithin A Against Alzheimer’S Disease, Dona P.W. Jayatunga, Eugene Hone, Binosha W.M.A. Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins
A Synergistic Combination Of Dha, Luteolin, And Urolithin A Against Alzheimer’S Disease, Dona P.W. Jayatunga, Eugene Hone, Binosha W.M.A. Fernando, Manohar L. Garg, Giuseppe Verdile, Ralph N. Martins
Research outputs 2022 to 2026
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common form of dementia worldwide. The classical AD brain is characterized by extracellular deposition of amyloid-β (Aβ) protein aggregates as senile plaques and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated forms of the microtubule-associated protein Tau. There has been limited success in clinical trials for some proposed therapies for AD, so attention has been drawn toward using alternative approaches, including prevention strategies. As a result, nutraceuticals have become attractive compounds for their potential neuroprotective capabilities. The objective of the present study was to derive a synergistic nutraceutical combination in …
Evaluation Of Virtual Screening Strategies For The Identification Of Γ-Secretase Inhibitors And Modulators, Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino
Evaluation Of Virtual Screening Strategies For The Identification Of Γ-Secretase Inhibitors And Modulators, Alicia Ioppolo, Melissa Eccles, David Groth, Giuseppe Verdile, Mark Agostino
Research outputs 2022 to 2026
γ-Secretase is an intramembrane aspartyl protease that is important in regulating normal cell physiology via cleavage of over 100 transmembrane proteins, including Amyloid Precursor Protein (APP) and Notch family receptors. However, aberrant proteolysis of substrates has implications in the progression of disease pathologies, including Alzheimer’s disease (AD), cancers, and skin disorders. While several γ-secretase inhibitors have been identified, there has been toxicity observed in clinical trials associated with non-selective enzyme inhibition. To address this, γ-secretase modulators have been identified and pursued as more selective agents. Recent structural evidence has provided an insight into how γ-secretase inhibitors and modulators are recognized …