McCusker Alzheimers Research Foundation

Perth, Australia

McCusker Alzheimers Research Foundation

Perth, Australia
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Brown B.M.,Murdoch University | Brown B.M.,Edith Cowan University | Brown B.M.,McCusker Alzheimers Research Foundation | Sohrabi H.R.,Edith Cowan University | And 32 more authors.
Alzheimer's and Dementia | Year: 2017

Introduction: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. Methods: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression. Results: No differences in brain amyloid load, CSF Aβ42, or CSF tau were observed between low and high exercise groups. Nevertheless, when examining only those already accumulating AD pathology (i.e., amyloid positive), low exercisers had higher mean levels of brain amyloid than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset was a significant predictor of brain amyloid levels. Discussion: Our findings indicate a relationship exists between self-reported exercise levels and brain amyloid in autosomal dominant AD mutation carriers. © 2017 the Alzheimer's Association.

Avdesh A.,Edith Cowan University | Avdesh A.,University of Western Australia | Chen M.,Edith Cowan University | Chen M.,McCusker Alzheimers Research foundation | And 16 more authors.
Journal of Visualized Experiments | Year: 2012

This protocol describes regular care and maintenance of a zebrafish laboratory. Zebrafish are now gaining popularity in genetics, pharmacological and behavioural research. As a vertebrate, zebrafish share considerable genetic sequence similarity with humans and are being used as an animal model for various human disease conditions. The advantages of zebrafish in comparison to other common vertebrate models include high fecundity, low maintenance cost, transparent embryos, and rapid development. Due to the spur of interest in zebrafish research, the need to establish and maintain a productive zebrafish housing facility is also increasing. Although literature is available for the maintenance of a zebrafish laboratory, a concise video protocol is lacking. This video illustrates the protocol for regular housing, feeding, breeding and raising of zebrafish larvae. This process will help researchers to understand the natural behaviour and optimal conditions of zebrafish husbandry and hence troubleshoot experimental issues that originate from the fish husbandry conditions. This protocol will be of immense help to researchers planning to establish a zebrafish laboratory, and also to graduate students who are intending to use zebrafish as an animal model.

Chatterjee P.,University of Western Australia | Chatterjee P.,McCusker Alzheimers Research Foundation | Chatterjee P.,The Cooperative Research Center for Mental Health | Chatterjee P.,Edith Cowan University | And 30 more authors.
Journal of Alzheimer's Disease | Year: 2016

Background and Objective: Aberrant lipid metabolism has been implicated in sporadic Alzheimer's disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD). Methods: Study participants evaluated were from the Perth and Melbourne sites of the Dominantly Inherited Alzheimer Network (DIAN) study. Plasma phospholipid and sphingolipid profiles were measured using liquid chromatography coupled with mass spectrometry in 20 PSEN1 mutation carriers (MC; eight of whom were symptomatic and twelve asymptomatic, based on Clinical Dementia Rating scores) and compared with six non carriers (NC) using linear mixed models. Further, AD gold standard biomarker data obtained from the DIAN database were correlated with lipid species significantly altered between MC and NC, using Spearman's correlation coefficient. Results: One-hundred and thirty-nine plasma phospholipid and sphingolipid species were measured. Significantly altered species in MC compared to NC primarily belonged to choline and ethanolamine containing phospholipid classes and ceramides. Further phosphatidylcholine species (34:6, 36:5, 40:6) correlated with cerebrospinal fluid tau (p < 0.05), and plasmalogen ethanolamine species (34:2, 36:,4) correlated with both cerebrospinal fluid tau and brain amyloid load within the MC group (p < 0.05). Conclusion: These findings indicate altered phospholipid and sphingolipid metabolism in ADAD and provide insight into the pathomolecular changes occurring with ADAD pathogenesis. Further, findings reported in this study allow comparison of lipid alterations in ADAD with those reported previously in sporadic AD. The findings observed in the current pilot study warrant validation in the larger DIAN cohort. © 2016 - IOS Press and the authors. All rights reserved.

Brown B.M.,Edith Cowan University | Bourgeat P.,Edith Cowan University | Peiffer J.J.,Austin Health | Burnham S.,CSIRO | And 14 more authors.
Neurology | Year: 2014

Objective: To investigate the association between habitual physical activity levels and brain temporal lobe volumes, and the interaction with the brain-derived neurotrophic factor (BDNF) Val66- Met polymorphism. Methods: This study is a cross-sectional analysis of 114 cognitively healthy men and women aged 60 years and older. Brain volumes quantified by MRI were correlated with self-reported physical activity levels. The effect of the interaction between physical activity and the BDNF Val66Met polymorphism on brain structure volumes was assessed. Post hoc analyses were completed to evaluate the influence of the APOE e4 allele on any found associations. Results: The BDNF Val66Met polymorphism interacted with physical activity to be associated with hippocampal (b 5 20.22, p 5 0.02) and temporal lobe (b 5 20.28, p 5 0.003) volumes. In Val/Val homozygotes, higher levels of physical activity were associated with larger hippocampal and temporal lobe volumes, whereas in Met carriers, higher levels of physical activity were associated with smaller temporal lobe volume. Conclusion: The findings from this study support higher physical activity levels in the potential attenuation of age- And disease-related hippocampal and temporal lobe volume loss in Val/Val homozygotes. © 2014 American Academy of Neurology.

Fernando W.M.A.D.B.,Edith Cowan University | Fernando W.M.A.D.B.,McCusker Alzheimers Research Foundation | Martins I.J.,Edith Cowan University | Martins I.J.,McCusker Alzheimers Research Foundation | And 10 more authors.
British Journal of Nutrition | Year: 2015

Coconut, Cocos nucifera L., is a tree that is cultivated to provide a large number of products, although it is mainly grown for its nutritional and medicinal values. Coconut oil, derived from the coconut fruit, has been recognised historically as containing high levels of saturated fat; however, closer scrutiny suggests that coconut should be regarded more favourably. Unlike most other dietary fats that are high in long-chain fatty acids, coconut oil comprises medium-chain fatty acids (MCFA). MCFA are unique in that they are easily absorbed and metabolised by the liver, and can be converted to ketones. Ketone bodies are an important alternative energy source in the brain, and may be beneficial to people developing or already with memory impairment, as in Alzheimer's disease (AD). Coconut is classified as a highly nutritious 'functional food'. It is rich in dietary fibre, vitamins and minerals; however, notably, evidence is mounting to support the concept that coconut may be beneficial in the treatment of obesity, dyslipidaemia, elevated LDL, insulin resistance and hypertension - these are the risk factors for CVD and type 2 diabetes, and also for AD. In addition, phenolic compounds and hormones (cytokinins) found in coconut may assist in preventing the aggregation of amyloid-β peptide, potentially inhibiting a key step in the pathogenesis of AD. The purpose of the present review was to explore the literature related to coconut, outlining the known mechanistic physiology, and to discuss the potential role of coconut supplementation as a therapeutic option in the prevention and management of AD. Copyright © The Authors 2015.

Brown B.M.,University of Western Australia | Brown B.M.,Edith Cowan University | Brown B.M.,McCusker Alzheimers Research Foundation | Peiffer J.J.,Murdoch University | And 3 more authors.
Molecular Psychiatry | Year: 2013

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes. © 2013 Macmillan Publishers Limited.

Gupta V.B.,Edith Cowan University | Gupta V.B.,McCusker Alzheimers Research Foundation | Wilson A.C.,Edith Cowan University | Wilson A.C.,McCusker Alzheimers Research Foundation | And 26 more authors.
Alzheimer's Research and Therapy | Year: 2015

Introduction: Alzheimer's disease (AD) is a growing socioeconomic problem worldwide. Early diagnosis and prevention of this devastating disease have become a research priority. Consequently, the identification of clinically significant and sensitive blood biomarkers for its early detection is very important. Apolipoprotein E (APOE) is a well-known and established genetic risk factor for late-onset AD; however, the impact of the protein level on AD risk is unclear. We assessed the utility of plasma ApoE protein as a potential biomarker of AD in the large, well-characterised Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) cohort. Methods: Total plasma ApoE levels were measured at 18-month follow-up using a commercial bead-based enzyme-linked immunosorbent assay: the Luminex xMAP human apolipoprotein kit. ApoE levels were then analysed between clinical classifications (healthy controls, mild cognitive impairment (MCI) and AD) and correlated with the data available from the AIBL cohort, including but not limited to APOE genotype and cerebral amyloid burden. Results: A significant decrease in ApoE levels was found in the AD group compared with the healthy controls. These results validate previously published ApoE protein levels at baseline obtained using different methodology. ApoE protein levels were also significantly affected, depending on APOE genotypes, with ε2/ε2 having the highest protein levels and ε4/ε4 having the lowest. Plasma ApoE levels were significantly negatively correlated with cerebral amyloid burden as measured by neuroimaging. Conclusions: ApoE is decreased in individuals with AD compared with healthy controls at 18-month follow-up, and this trend is consistent with our results published at baseline. The influence of APOE genotype and sex on the protein levels are also explored. It is clear that ApoE is a strong player in the aetiology of this disease at both the protein and genetic levels. © 2015 Gupta et al.; licensee BioMed Central.

Martins I.J.,Edith Cowan University | Martins I.J.,The University ofWestern Australia | Martins I.J.,Mccusker Alzheimers Research Foundation
International Journal of Molecular Sciences | Year: 2015

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 membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Martins I.J.,Edith Cowan University | Martins I.J.,University of Western Australia | Gupta V.,Edith Cowan University | Gupta V.,University of Western Australia | And 6 more authors.
Current Proteomics | Year: 2014

Proteomics has advanced and identified various plasma proteins that may be implicated in lesions in brains from neurodegenerative individuals. Apolipoprotein E and amyloid beta are amongst the many candidate proteins identified in common neurodegenerative disorders with effects by diet and nutriproteomics on the interactions of apo E and amyloid beta. The purpose of this review paper is to specify the role of proteins and lipoproteins and their effects on hepatic amyloid beta clearance that are important to brain amyloidosis. In recent and historical research provided in various research papers the blood brain barrier (BBB) is abnormal in neurodegenerative disease and proteins and oxidized lipids leak across the BBB. The improved scientific understanding of apo E/amyloid beta interactions identifies modulations in protein structure and lipid:protein interactions induced by nutrients and has become important to peripheral amyloid beta metabolism. Hepatic acute phase proteins induced by diet, inflammation and oxidative stress are connected to the pathophysiology of neurotoxic diseases. Oxidative stress induced by high cholesterol diets can cause electrostatic alterations in amyloid oligomers accompanied with alterations in oxidized lipids and acute phase proteins. Recent progress in proteomics with relevance to Alzheimer’s disease has led to the identification of acute phase proteins and include pentraxins that regulate or reduce amyloid beta sizes that are related to membrane permeability and disruption. In this review research papers identify acute phase biomarkers that are involved in the alterations of amyloid beta oligomers in obesity and diabetes with increased BBB permeability and central nervous system disorders. © 2014 Bentham Science Publishers.

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