Medicine and Health Sciences Commons^™

Predicting Neurodegeneration From Sleep Related Biofluid Changes, Yue Yang, Woojin S. Kim, Johannes C. Michaelian, Simon J. G. Lewis, Craig L. Phillips, Angela L. D'Rozario, Pratishtha Chatterjee, Ralph N. Martins, Ron Grunstein, Glenda M. Halliday, Sharon L. Naismith

Research outputs 2022 to 2026

Sleep-wake disturbances are common in neurodegenerative diseases and may occur years before the clinical diagnosis, potentially either representing an early stage of the disease itself or acting as a pathophysiological driver. Therefore, discovering biomarkers that identify individuals with sleep-wake disturbances who are at risk of developing neurodegenerative diseases will allow early diagnosis and intervention. Given the association between sleep and neurodegeneration, the most frequently analyzed fluid biomarkers in people with sleep-wake disturbances to date include those directly associated with neurodegeneration itself, such as neurofilament light chain, phosphorylated tau, amyloid-beta and alpha-synuclein. Abnormalities in these biomarkers in patients with sleep-wake disturbances …

Sixteen-Year Longitudinal Evaluation Of Blood-Based Dna Methylation Biomarkers For Early Prediction Of Alzheimer's Disease, Fernanda Schäfer Hackenhaar, Maria Josefsson, Annelie Nordin Adolfsson, Mattias Landfors, Karolina Kauppi, Tenielle Porter, Lidija Milicic, Simon M. Laws, Magnus Hultdin, Rolf Adolfsson, Sofie Degerman, Sara Pudas, Australian Imaging Biomarkers And Lifestyle Study

Research outputs 2022 to 2026

BACKGROUND: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. OBJECTIVE: Testing long-term predictive ability ( > 15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. METHODS: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares …

Alzheimer's Disease Research Progress In Australia: The Alzheimer's Association International Conference Satellite Symposium In Sydney, Claire E. Sexton, Kaarin J. Anstey, Filippo Baldacci, C. J. Barnum, Anna M. Barron, Kaj Blennow, Henry Brodaty, Samantha Burnham, Fanny M. Elahi, Jürgen Götz, Yun-Hee Jeon, Maya Koronyo-Hamaoui, Susan M. Landau, Nicola T. Lautenschlager, Simon M. Laws, Darren M. Lipnicki, Hanzhang Lu, Colin L. Masters, Wendy Moyle, Akinori Nakamura, Giulio Maria Pasinetti, Naren Rao, Christopher Rowe, Perminder S. Sachdev, Peter R. Schofield, Einar M. Sigurdsson

Research outputs 2014 to 2021

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms …

Comparison Of Circulating Tumour Dna And Extracellular Vesicle Dna By Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers Of Disease In A Breast Cancer Patient, Olivia Ruhen, Bob Mirzai, Michael E. Clark, Bella Nguyen, Carlos Salomon, Wendy Erber, Katie Meehan

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both …

Fifteen Years Of The Australian Imaging, Biomarkers And Lifestyle (Aibl) Study: Progress And Observations From 2,359 Older Adults Spanning The Spectrum From Cognitive Normality To Alzheimer's Disease, Christopher Fowler, Stephanie R. Rainey-Smith, Sabine Bird, Julia Bomke, Pierrick Bourgeat, Belinda M. Brown, Samantha C. Burnham, Ashley I. Bush, Carolyn Chadunow, Steven Collins, James Doecke, Vincent Doré, Kathryn A. Ellis, Lis Evered, Amir Fazlollahi, Jurgen Fripp, Samantha L. Gardener, Simon Gibson, Robert Grenfell, Elise Harrison, Richard Head, Liang Jin, Adrian Kamer, Fiona Lamb, Nicola T. Lautenschlager, Simon M. Laws, Qiao-Xin Li, Lucy Lim, Yen Ying Lim, Andrea Louey, S. Lance Macaulay, Lucy Mackintosh, Ralph N. Martins, Paul Maruff, Colin L. Masters, Simon Mcbride, Lidija Milicica, Madeline Peretti, Kelly Pertile, Tenielle Porter, Morgan Radler, Alan Rembach, Joanne Robertson, Mark Rodrigues, Christopher C. Rowe, Rebecca Rumble, Olivier Salvado, Greg Savage, Brendan Silbert, Magdalene Soh, Hamid R. Sohrabi, Kevin Taddei, Tania Taddei, Christine Thai, Brett Trounson, Regan Tyrrell, Michael Vacher, Shiji Varghese, Victor L. Villemagne, Michael Weinborn, Michael Woodward, Ying Xia, David Ames, Aibl Investigators

Research outputs 2014 to 2021

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). Objective: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. Methods: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance …

Core Alzheimer’S Disease Cerebrospinal Fluid Biomarker Assays Are Not Affected By Aspiration Or Gravity Drip Extraction Methods, James D. Doecke, Cindy Francois, Christopher J. Fowler, Erik Stoops, Pierrick Bourgeat, Stephanie R. Rainey-Smith, Qiao-Xin Li, Colin L. Masters, Ralph N. Martins, Victor L. Villemagne, Steven J. Collins, Hugo Marcel Vanderstichele

Research outputs 2014 to 2021

Background: CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration. Methods: Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6). Results: High biomarker concordance between extraction methods was seen …

Plasma Apolipoprotein J As A Potential Biomarker For Alzheimer's Disease: Australian Imaging, Biomarkers And Lifestyle Study Of Aging, Veer Gupta, James D. Doecke, Eugene Hone, Steve Pedrini, Simon M. Laws, Madhav Thambisetty, Ashley Bush,, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Stuart Lance Macaulay, Alan Rembach, Stephanie R. Rainey-Smith, Ralph N. Martins

Research outputs 2014 to 2021

Introduction:

For early detection of Alzheimer's disease (AD), the field needs biomarkers that can be used to detect disease status with high sensitivity and specificity. Apolipoprotein J (ApoJ, also known as clusterin) has long been associated with AD pathogenesis through various pathways. The aim of this study was to investigate the potential of plasma apoJ as a blood biomarker for AD.

Methods:

Using the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the present study assayed plasma apoJ levels over baseline and 18 months in 833 individuals. Plasma ApoJ levels were analyzed with respect to clinical classification, age, gender, …

Altered Cytological Parameters In Buccal Cells From Individuals With Mild Cognitive Impairment And Alzheimer's Disease, Maxime François, Wayne Leifert, Jane Hecker, Jeffrey Faunt, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Previous studies have shown that mild cognitive impairment (MCI) may be reflective of the early stages of more pronounced neurodegenerative disorders such as Alzheimer's disease (AD). There is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritized for primary preventative measures. The hypothesis was that a minimally invasive approach using cytological markers in isolated buccal mucosa cells can be used to identify individuals of both MCI and AD. An automated buccal cell assay was developed using laser scanning cytometry (LSC) to …