Medicine and Health Sciences Commons^™

The Relationship Between Physical Activity, Apolipoprotein E Ε4 Carriage, And Brain Health, Jaisalmer De Frutos-Lucas, Pablo Cuesta, David López-Sanz, Africa Peral-Suárez, Esther Cuadrado-Soto, Federico Ramírez-Toraño, Belinda M. Brown, Juan M. Serrano, Simon M. Laws, Inmaculada C. Rodríguez-Rojo, Juan Verdejo-Román, Ricardo Bruña, Maria L. Delgado-Losada, Ana Barabash, Ana M. López-Sobaler, Ramon López-Higes, Alberto Marcos, Fernando Maestú

Research outputs 2014 to 2021

BACKGROUND: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer's disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. METHOD: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. …

Serum Hepcidin Levels In Cognitively Normal Older Adults With High Neocortical Amyloid-Beta Load, Pratishtha Chatterjee, Maryam Mohammadi, Kathryn Goozee, Tejal Shah, Hamid R. Sohrabi, Cintia B. Dias, Kaikai Shen, Prita R. Asih, Preeti Dave, Steve Pedrini, Nicholas J. Ashton, Abdul Hye, Kevin Taddei, David B. Lovejoy, Henrik Zetterberg, Kaj Blennow, Ralph Martins

Research outputs 2014 to 2021

Background/Objective:

Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer’s disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-β load (NAL).

Methods:

Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65–90 years were measured using ELISA. To evaluate NAL, all …

Relationships Between Plasma Lipids Species, Gender, Risk Factors And Alzheimer’S Disease, Wei Ling Florence Lim, Kevin Huynh, Pratishtha Chatterjee, Ian Martins, Kaushala S. Jayawardana, Corey Giles, Natalie A. Mellett, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Brian G. Drew, Colin L. Masters, Peter J. Meikle, Ralph Martins, Australian Imaging, Biomarker & Lifestyle Research Group

Research outputs 2014 to 2021

Background:

Lipid metabolism is altered in Alzheimer’s disease (AD); however, the relationship between AD risk factors (age, APOE ɛ4, and gender) and lipid metabolism is not well defined.

Objective:

We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals.

Methods:

We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore …

Docosahexaenoic Acid-Rich Fish Oil Supplementation Reduces Kinase Associated With Insulin Resistance In Overweight And Obese Midlife Adults, Rohith N. Thota, Jessica I. Rosato, Tracy L. Burrows, Cintia B. Dias, Kylie A. Abbott, Ralph N. Martins, Manohar L. Garg

Research outputs 2014 to 2021

Targeting kinases linked to insulin resistance (IR) and inflammation may help in reducing the risk of type 2 diabetes (T2D) and Alzheimer’s disease (AD) in its early stages. This study aimed to determine whether DHA-rich fish oil supplementation reduces glycogen synthase kinase (GSK-3), which is linked to both IR and AD. Baseline and post-intervention plasma samples from 58 adults with abdominal obesity (Age: 51.7 ± 1.7 years, BMI: 31.9 ± 0.8 kg/m2) were analysed for outcome measures. Participants were allocated to 2 g DHA-rich fish oil capsules (860 mg DHA + 120 mg EPA) (n = 31) or placebo capsules …

Copper Toxicity Links To Pathogenesis Of Alzheimer’S Disease And Therapeutics Approaches, Hafza Wajeeha Ejaz, Wei Wang, Minglin Lang

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of …

Bilingualism Is Associated With A Delayed Onset Of Dementia But Not With A Lower Risk Of Developing It: A Systematic Review With Meta-Analyses, Stefano Brini, Hamid R. Sohrabi, Jeffrey J. Hebert, Mitchell R.L. Forrest, Matti Laine, Heikki Hämäläinen, Mira Karrasch, Jeremiah Peiffer, Ralph Martins, Timothy J. Fairchild

Research outputs 2014 to 2021

Some studies have linked bilingualism with a later onset of dementia, Alzheimer’s disease (AD), and mild cognitive impairment (MCI). Not all studies have observed such relationships, however. Differences in study outcomes may be due to methodological limitations and the presence of confounding factors within studies such as immigration status and level of education. We conducted the first systematic review with meta-analysis combining cross-sectional studies to explore if bilingualism might delay symptom onset and diagnosis of dementia, AD, and MCI. Primary outcomes included the age of symptom onset, the age at diagnosis of MCI or dementia, and the risk of developing …

Validation And Reliability Of The Alzheimer’S Disease-Commonwealth Scientific And Industrial Research Organisation Food Frequency Questionnaire, Samantha L. Gardener, Philippa Lyons-Wall, Ralph Martins, Stephanie Rainey-Smith

Research outputs 2014 to 2021

Accuracy in measuring intake of dietary constituents is an important issue in studies reporting the associations between diet and chronic diseases. We modified a Commonwealth Scientific and Industrial Research Organisation (CSIRO) food frequency questionnaire (FFQ) to include foods of interest in the field of Alzheimer’s disease (AD) research. The aim of the current study was to determine the reliability and validity of the AD-CSIROFFQ in 148 cognitively normal older adults. The AD-CSIROFFQ was completed before and after completion of a four-day weighed food record. Of the 508 food and beverage items reported, 309 had sufficient consumption levels for analysis of …

Autophagy Modulation As A Treatment Of Amyloid Diseases, Zoe Mputhia, Eugene Hone, Timir Tripathi, Tim Sargeant, Ralph Martins, Prashant Bharadwaj

Research outputs 2014 to 2021

Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer's disease (AD), Parkinson's disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic …

Validation Of A Priori Candidate Alzheimer’S Disease Snps With Brain Amyloid-Beta Deposition, Michael Vacher, Tenielle Porter, Victor L. Villemagne, Lidija Milicic, Madeline Peretti, Christopher C. Fowler, Ralph Martins, Stephanie Rainey-Smith, David Ames, Colin L. Masters, Christopher C. Rowe, James D. Doecke, Simon M. Laws

Research outputs 2014 to 2021

The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer’s disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain unclear. In this study, we sought to identify associations between Aβ deposition and an a priori evidence based set of 1610 genetic markers, genotyped from 505 unrelated individuals (258 Aβ+ and 247 Aβ−) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We found statistically significant associations for 6 markers located within intronic regions of 6 genes, including AC103796.1-BDNF, PPP3R1, …

Rates Of Age- And Amyloid Β-Associated Cortical Atrophy In Older Adults With Superior Memory Performance, Christa Dang, Nawaf Yassi, Karra D. Harrington, Ying Xia, Yen Ying Lim, David Ames, Simon M. Laws, Martha Hickey, Stephanie Rainey-Smith, Hamid R. Sohrabi, James D. Doecke, Jurgen Fripp, Olivier Salvado, Peter J. Snyder, Michael Weinborn, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Paul Maruff

Research outputs 2014 to 2021

Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid b (Ab) deposition (Ab1) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Ab-associated neurodegeneration. Methods: Neuropsychologically defined SuperAgers (n 5 172) and cognitively normal for age (n 5 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Ab status. Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Ab1. …

Application Of The Nia-Aa Research Framework: Towards A Biological Definition Of Alzheimer’S Disease Using Cerebrospinal Fluid Biomarkers In The Aibl Study, S. C. Burnham, P. M. Coloma, Q.-X. Li, S. Collins, G. Savage, S. Laws, J. Doecke, P. Maruff, R. N. Martins, D. Ames, C. C. Rowe, C. L. Masters, V. L. Villemagne

Research outputs 2014 to 2021

BACKGROUND: The National Institute on Aging and Alzheimer’s Association (NIA-AA) have proposed a new Research Framework: Towards a biological definition of Alzheimer’s disease, which uses a three-biomarker construct: Aß-amyloid, tau and neurodegeneration AT(N), to generate a biomarker based definition of Alzheimer’s disease. OBJECTIVES: To stratify AIBL participants using the new NIA-AA Research Framework using cerebrospinal fluid (CSF) biomarkers. To evaluate the clinical and cognitive profiles of the different groups resultant from the AT(N) stratification. To compare the findings to those that result from stratification using two-biomarker construct criteria (AT and/or A(N)). DESIGN: Individuals were classified as being positive or negative …

A Polygenic Risk Score Derived From Episodic Memory Weighted Genetic Variants Is Associated With Cognitive Decline In Preclinical Alzheimer’S Disease, Tenielle Porter, Samantha C. Burnham, Greg Savage, Yen Ying Lim, Paul Maruff, Lidija Milicic, Madeline Peretti, David Ames, Colin L. Masters, Ralph N. Martins, Stephanie Rainey-Smith, Christopher C. Rowe, Olivier Salvado, Kevin Taddei, David Groth, Guiseppe Verdile, Victor L. Villemagne, Simon M. Laws

Research outputs 2014 to 2021

Studies of Alzheimer’s disease risk-weighted polygenic risk scores (PRSs) for cognitive performance have reported inconsistent associations. This inconsistency is particularly evident when PRSs are assessed independent of APOE genotype. As such, the development and assessment of phenotype-specific weightings to derive PRSs for cognitive decline in preclinical AD is warranted. To this end a episodic memory-weighted PRS (emPRS) was derived and assessed against decline in cognitive performance in 226 healthy cognitively normal older adults with high brain Aβ-amyloid burden participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. The effect size for decline in a verbal episodic memory …

Alzheimer's Disease: A Journey From Amyloid Peptides And Oxidative Stress, To Biomarker Technologies And Disease Prevention Strategies-Gains From Aibl And Dian Cohort Studies, Ralph Martins, Victor Villemagnen, Hamid R. Sohrabi, Pratishtha Chatterjee, Tejal M. Shah, Giuseppe Verdile, Paul Fraser, Kevin Taddei, Veer Gupta, Stephanie Rainey-Smith, Eugene Hone, Steve Pedrini, Wei L. Lim, Ian Martins, Shaun Frost, Sunil Gupta, Sid O’Bryant, Alan Rembach, David Ames, Kathryn Ellis, Stephanie J. Fuller, Belinda Brown, Samantha Gardener, Binosha Fernando, Prashant Bharadwaj, Samantha Burnham, Simon Laws, Anna M. Barron, Kathryn Goozee, Eka J. Wahjoepramono, Prita R. Asih, James D. Doecke, Olivier Salvado, Ashley I. Bush, Christopher C. Rowe, Samuel E. Gandy, Colin L. Masters

Research outputs 2014 to 2021

Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group inWestern Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the …

The Role Of Clinical Proteomics, Lipidomics, And Genomics In The Diagnosis Of Alzheimer's Disease, Ian James Martins

Research outputs 2014 to 2021

The early diagnosis of Alzheimer’s disease (AD) has become important to the reversal and treatment of neurodegeneration, which may be relevant to premature brain aging that is associated with chronic disease progression. Clinical proteomics allows the detection of various proteins in fluids such as the urine, plasma, and cerebrospinal fluid for the diagnosis of AD. Interest in lipidomics has accelerated with plasma testing for various lipid biomarkers that may with clinical proteomics provide a more reproducible diagnosis for early brain aging that is connected to other chronic diseases. The combination of proteomics with lipidomics may decrease the biological variability between …

Changes In The Plasma Proteome At Asymptomatic And Symptomatic Stages Of Autosomal Dominant Alzheimer's Disease, Julia Muenchhoff, Anne Poljak, Anbupalam Thalamuthu, Veer Gupta, Pratishtha Chatterjee, Mark Raftery, Colin Masters, John Morris, Randall Bateman, Anne Fagan, Ralph Martins, Perminder Sachdev

Research outputs 2014 to 2021

The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose …

Examining The Potential Clinical Value Of Curcumin In The Prevention And Diagnosis Of Alzheimer's Disease, K. G. Goozee, T. M. Shah, Hamid R. Sohrabi, Stephanie Rainey-Smith, B. Brown, Guiseppe Verdile, Ralph Martins

Research outputs 2014 to 2021

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer’s disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to …

The Effects Of Testosterone Supplementation On Cognitive Functioning In Older Men, Eka Wahjoepramono, Prita Asih, Vilia Aniwiyanti, Kevin Taddei, Satvinder Dhaliwal, Stephanie Fuller, Jonathan Foster, Malcolm Carruthers, Giuseppe Verdile, Hamid R. Sohrabi, Ralph Martins

Research outputs 2014 to 2021

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer’s disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 …

Aβ-Related Memory Decline In Apoe Ε4 Noncarriers: Implications For Alzheimer Disease, Yen Ying Lim, Simon Laws, Victor Villemagne, Robert Pietrzak, Tenielle Porter, David Ames, Christoher Fowler, Stephanie Rainey-Smith, Peter Snyder, Ralph Martins, Olivier Salvado, Pierrick Bourgeat, Christopher Rowe, Colin Masters, Paul Maruff

Research outputs 2014 to 2021

Objective:

As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN).

Methods:

CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.

Results:

Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of …

Overnutrition Determines Lps Regulation Of Mycotoxin Induced Neurotoxicity In Neurodegenerative Diseases, Ian J. Martins

Research outputs 2014 to 2021

Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and …

Decreased Serum Zinc Is An Effect Of Ageing And Not Alzheimer's Disease, Alan Rembach, Dominic Hare, James Doecke, Samantha Burnham, Irene Volitakis, Christopher Fowler, Robert Cherny, Catriona Mclean, Rudolf Grimm, Ralph N. Martins, David Ames, Colin Masters, Ashley Bush, Blaine Roberts

Research outputs 2014 to 2021

We examined the distribution of zinc in the periphery (erythrocytes and serum) in a large, well-characterised cohort, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, in order to determine if there is systemic perturbation in zinc homeostasis in Alzheimer’s disease (AD). We observed an age dependent decrease in serum zinc of approximately 0.4% per year. When correcting for the age dependent decline in serum zinc no significant difference between healthy controls (HC), mildly cognitively impaired (MCI) or AD subjects was observed.

A Blood-Based Predictor For Neocortical Aβ Burden In Alzheimer's Disease: Results From The Aibl Study, Samantha Burnham, Noel Faux, William Wilson, Simon Laws, David Ames, Justin Bedo, Ashley Bush, James Doecke, Kathryn Ellis, Richard Head, Gareth Jones, Harri Kiiveri, Ralph N. Martins, Alan Rembach, Christopher Rowe, Olivier Salvado, S Lance Macaulay, Colin Masters, Victor Villemagne

Research outputs 2013

Dementia is a global epidemic with Alzheimer’s disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in …

Dietary Patterns Associated With Alzheimer's Disease And Related Chronic Disease Risk: A Review, Samantha L. Gardener, Stephanie R. Rainey-Smith, Jennifer Keogh, Suzanne Mathieson, Ralph N. Martins

Research outputs 2013

The world’s population is growing older due to improved healthcare and nutrition. As a result, Alzheimer’s disease (AD) prevalence is rapidly increasing. The focus of the current research climate is shifting from understanding AD pathology and diagnosis to primary prevention and intervention strategies. Diet represents one potential intervention strategy accessible to all. Accumulating evidence suggests diet plays a major role in risk and development of AD and AD-related chronic diseases of the periphery like cardiovascular disease (CVD) and diabetes. This paper reviews studies that have explored the relationship between “a priori” dietary patterns, AD and AD-related chronic disease risk. The …

Adherence To A Mediterranean Diet And Alzheimer's Disease Risk In An Australian Population, Samantha Gardener, Y Gu, Stephanie Rainey-Smith, J B Keogh, P M Clifton, S L Mathieson, Kevin Taddei, Alinda Mondal, Vanessa Ward, N Scarmeas, M Barnes, K Ellis, R Head, C 0 Masters, D Ames, S 0 Macaulay, C 0 Rowe, C Szoeke, Ralph Martins

Research outputs 2012

The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer’s disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher …