The McCusker Alzheimers Research Foundation

Nedlands, Australia

The McCusker Alzheimers Research Foundation

Nedlands, Australia
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PubMed | Washington University in St. Louis, The McCusker Alzheimers Research Foundation, University of Western Australia, CAS Institute of Genetics and Developmental Biology and 4 more.
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2016

Aberrant lipid metabolism has been implicated in sporadic Alzheimers disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD).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 Spearmans correlation coefficient.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).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.


Sohrabi H.R.,Edith Cowan University | Sohrabi H.R.,The McCusker Alzheimers Research Foundation | Sohrabi H.R.,University of Western Australia | Bates K.A.,The McCusker Alzheimers Research Foundation | And 38 more authors.
Frontiers in Aging Neuroscience | Year: 2015

Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34-87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms. © 2015 Sohrabi, Bates, Weinborn, Bucks, Rainey-Smith, Rodrigues, Bird, Brown, Beilby, Howard, Criddle, Wraith, Taddei, Martins, Paton, Shah, Dhaliwal, Mehta, Foster, Martins, Lautenschlager, Mastaglia, Laws and Martins.


Frost S.,The McCusker Alzheimers Research Foundation
Current Alzheimer research | Year: 2013

A screening process that could provide early and accurate diagnosis or prognosis for Alzheimer's disease (AD) would enable earlier intervention, and enable current and future treatments to be more effective. Ocular pathology and changes to vision and ocular function are being investigated for early detection and monitoring of AD. To explore the relationship between pupil flash response (PFR) parameters, AD and brain amyloid plaque burden. Nineteen AD and seventy healthy control (HC) participants were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. The potential correlations between PFR parameters and 1) AD and 2) brain amyloid plaque burden in the HC group (as a pre-clinical feature of AD), were investigated in this study. Our results demonstrate statistically significant relationships between PFR parameters, neocortical plaque burden and AD. A logistical model combining PFR parameters provided AD-classification performance with sensitivity 84.1%, specificity 78.3% and area under the curve 89.6%. Furthermore, some of the AD specific PFR parameters were also associated with neocortical plaque burden in pre-clinical AD. These PFR changes show potential as an adjunct for noninvasive, cost-effective screening for pre-clinical AD.


PubMed | The McCusker Alzheimers Research Foundation
Type: Journal Article | Journal: Current Alzheimer research | Year: 2013

A screening process that could provide early and accurate diagnosis or prognosis for Alzheimers disease (AD) would enable earlier intervention, and enable current and future treatments to be more effective. Ocular pathology and changes to vision and ocular function are being investigated for early detection and monitoring of AD.To explore the relationship between pupil flash response (PFR) parameters, AD and brain amyloid plaque burden.Nineteen AD and seventy healthy control (HC) participants were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. The potential correlations between PFR parameters and 1) AD and 2) brain amyloid plaque burden in the HC group (as a pre-clinical feature of AD), were investigated in this study.Our results demonstrate statistically significant relationships between PFR parameters, neocortical plaque burden and AD. A logistical model combining PFR parameters provided AD-classification performance with sensitivity 84.1%, specificity 78.3% and area under the curve 89.6%. Furthermore, some of the AD specific PFR parameters were also associated with neocortical plaque burden in pre-clinical AD.These PFR changes show potential as an adjunct for noninvasive, cost-effective screening for pre-clinical AD.

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