Nervous System Diseases Commons^™

Plasma High-Density Lipoprotein Cargo Is Altered In Alzheimer's Disease And Is Associated With Regional Brain Volume, Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley I. Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) …

Plasma Glial Fibrillary Acidic Protein Is Elevated In Cognitively Normal Older Adults At Risk Of Alzheimer’S Disease, Pratishtha Chatterjee, Steve Pedrini, Erik Stoops, Kathryn Goozee, Victor L. Villemagne, Prita R. Asih, Inge M. W. Verberk, Preeti Dave, Kevin Taddei, Hamid R. Sohrabi, Henrik Zetterberg, Kaj Blennow, Charlotte E. Teunissen, Hugo M. Vanderstichele, Ralph N. Martins

Research outputs 2014 to 2021

© 2021, The Author(s). Glial fibrillary acidic protein (GFAP), an astrocytic cytoskeletal protein, can be measured in blood samples, and has been associated with Alzheimer’s disease (AD). However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-β (Aβ) load. Cross-sectional analyses were carried out for plasma GFAP and plasma Aβ1–42/Aβ1–40 ratio, a blood-based marker associated with brain Aβ load, in participants (65–90 years) categorised into low (Aβ−, n = 63) and high (Aβ+, n = 33) brain Aβ load groups via Aβ positron emission tomography. Plasma GFAP, Aβ1–42, and Aβ1–40 …

Asymmetric Thinning Of The Cerebral Cortex Across The Adult Lifespan Is Accelerated In Alzheimer’S Disease, James M. Roe, Didac Vidal-Piñeiro, Øystein Sørensen, Andreas M. Brandmaier, Sandra Düzel, Hector A. Gonzalez, Rogier A. Kievit, Ethan Knights, Simone Kühn, Ulman Lindenberger, Athanasia M. Mowinckel, Lars Nyberg, Denise C. Park, Sara Pudas, Melissa M. Rundle, Kristine B. Walhovd, Anders M. Fjell, René Westerhausen, Colin L. Masters, Ashley I. Bush, Christopher Fowler, David Darby, Kelly Pertile, Carolina Restrepo, Blaine Roberts, Jo Robertson, Rebecca Rumble

Research outputs 2014 to 2021

© 2021, The Author(s). Aging and Alzheimer’s disease (AD) are associated with progressive brain disorganization. Although structural asymmetry is an organizing feature of the cerebral cortex it is unknown whether continuous age- and AD-related cortical degradation alters cortical asymmetry. Here, in multiple longitudinal adult lifespan cohorts we show that higher-order cortical regions exhibiting pronounced asymmetry at age ~20 also show progressive asymmetry-loss across the adult lifespan. Hence, accelerated thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This organizational principle showed high consistency across cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics …

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 …

The Utility Of Multidisciplinary Rehabilitation As A Treatment Strategy For Circadian Rhythm And Sleep Disturbances In Premanifest Huntington’S Disease, Danielle Megan Bartlett

Theses: Doctorates and Masters

Background: Huntington’s disease (HD) is a rare, neurodegenerative disease caused by an expanded cytosine-adenine-guanine (CAG) sequence in the Huntingtin gene, resulting in the production of an aberrant protein, mutant huntingtin (mHTT). The mHTT protein exhibits a toxic loss and gain in function, leading to degeneration of neurons in the brain. Consequently, the classic triad of motor, cognitive and mood features of the disease develop. Among the earliest features of HD are circadian rhythm and sleep disturbances. These anomalies present many years prior to formal clinical diagnosis of HD and, while it has been postulated that these disturbances arise as a …

Impaired Energy Metabolism: Involvement In Neurodegenerative Processes And Cns Ageing, Veer B. Gupta, Vivek K. Gupta

Research outputs 2014 to 2021

World is experiencing a consistent and steady increase in the ageing population with even higher proportional differences in the developed countries. Increase in ageing populations is directly correlated with the increased prevalence of age-related degenerative diseases of the central nervous system (CNS) such as Alzheimer’s disease and various other forms of dementias, stroke, Parkinson’s disease, retinal degenerative disorders, Huntington’s’ disease, multiple sclerosis, psychiatric and behavioural disorders amongst others.

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 Latrepirdine On Amyloid-Β Aggregation And Toxicity, Tenielle Porter, Prashant Bharadwaj, David Groth, Adrian Paxman, Simon Laws, Ralph Martins, Guiseppe Verdile

Research outputs 2014 to 2021

Latrepirdine (DimebonTM) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was …

The Clinical Utility Of Multidisciplinary Rehabilitation In Individuals With Huntington’S Disease, Travis Miles Cruickshank

Theses: Doctorates and Masters

Background

Huntington’s disease (HD) is a chronic neurodegenerative disorder characterised by a progressive loss of cognitive function, motor control and psychiatric features. Individuals also display a variety of systemic features. Progressive neuronal dysfunction and neuronal cell death are thought to underlie the onset and progression of many clinical features of HD.

Despite scientific progress, there is still no cure or disease modifying therapy for HD, and available pharmaceutical agents only provide partial relief of motor and psychiatric features. An emerging body of evidence indicates that lifestyle enrichment may delay the onset and progression of clinical features, and exert favourable effects …

The N-Glycosylation Of Immunoglobulin G As A Novel Biomarker Of Parkinson’S Disease, Alyce Christine Russell

Theses: Doctorates and Masters

For neurodegenerative diseases, interventions during the early stages of the disease, before significant neurodegeneration has occurred, are associated with an increased probability of slowing or halting the disease process. In order to intervene early, it is essential that an accurate diagnosis is obtained and that disease progression can be monitored. This is particularly relevant for Parkinson’s disease (PD; International Classification of Diseases version 10) because significant neurodegeneration has already occurred by the time the clinical motor symptoms are present. Therefore, the development of translatable, high-throughput biomarkers for large scale population screening is a crucial area of research. Of promise are …

Alzheimer's Disease Cerebrospinal Fluid Biomarkers Are Not Influenced By Gravity Drip Or Aspiration Extraction Methodology, Alan Rembach, Lisbeth A. Evered, Qiao-Xin Li, Tabitha Nash, Lesley Vidaurre, Christopher J. Fowler, Kelly K. Pertile, Rebecca L. Rumble, Brett O. Trounson, Sarah Maher, Francis Mooney, Maree Farrow, Kevin Taddei, Stephanie Rainey-Smith, Simon Laws, S. Lance Macaulay, William Wilson, David G. Darby, Ralph N. Martins, David Ames, Steven Collins, Brendon Silbert, Colin L. Masters, James D. Doecke

Research outputs 2014 to 2021

Introduction Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer’s disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results For the 44 total paired samples of gravity …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …