Medical Sciences Commons^™

Cerebrospinal Fluid Neurofilament Light Concentration Predicts Brain Atrophy And Cognition In Alzheimer's Disease, Kunal Dhiman, Veer Bala Gupta, Victor L. Villemagne, Dhamidhu Eratne, Petra L. Graham, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Ashley I. Bush, Christopher C. Rowe, Colin L. Masters, David Ames, Eugene Hone, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins

Research outputs 2014 to 2021

Introduction
This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.
Methods
CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).
Results
CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P < .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P< .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.
Discussion
CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.

Detection Of Hfe Haemochromatosis In The Clinic And Community Using Standard Erythrocyte Tests, Niwansa Adris, Simon Hazeldine, Peter Bentley, Debbie Trinder, Anita C.G. Chua, Lawrie W. Powell, Louise E. Ramm, Grant A. Ramm, John K. Olynyk

Research outputs 2014 to 2021

Detection of HFE Haemochromatosis (HH) is challenging in the absence of clinical features. HH subjects have elevated erythrocyte parameters compared to those without HH, but it remains unclear how this could be applied in clinical practice. Thus, we determined the sensitivity, specificity and clinical utility of erythrocyte parameters in 144 HH subjects with (n = 122) or without (n = 22) clinical and/or biochemical expression of iron overload, 1844 general population controls, and 700 chronic disease subjects. For both expressing and non-expressing HH subjects, the mean pre- and post-phlebotomy values of mean cell volume (MCV) and mean cell haemoglobin (MCH) …

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

Low-Level Cadmium Exposure And Cardiovascular Outcomes In Elderly Australian Women: A Cohort Study, Kane Deering, Anna C. Callan, Richard Prince, Wai Lim, Peter Thompson, Joshua Lewis, Andrea Hinwood, Amanda Devine

Research outputs 2014 to 2021

Background

Cadmium has been associated with increased risk of cardiovascular disease (CVD) in observational studies, however there has been a limited focus on this relationship in women.

Objectives

This study investigated the association of urinary cadmium (UCd) concentrations with CVD outcomes and all-cause mortality in elderly Western Australian (WA) women.

Methods

UCd excretion was measured at baseline in 1359 women, mean age 75.2 ± 2.7 years and 14.5 years of atherosclerotic vascular disease (ASVD) hospitalisations and deaths, including both the principle cause of death and all associated causes of death. Health outcome data were retrieved from the Western Australian Data …

Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins

Research outputs 2014 to 2021

Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid …

Circulating Tumour Dna: A Non-Invasive Biomarker For Melanoma, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Cutaneous melanoma accounts for 90% of all skin cancer deaths (Balch et al., 2010) and is responsible for 3.6% of deaths from cancer in Australia (Australian Institute of Health and Welfare, 2016). Whilst early detection and successful surgical removal of primary melanomas have improved survival rates (DeSantis et al., 2014), approximately 30% of these patients will have disease recurrence at some point in their lives (Soong et al., 1992; Soong et al., 1998). This is despite being considered disease free following treatment, which may have included surgical removal of the primary and/or its metastasis/es, radiation and/or systemic therapy. Whilst the …

The Cryopreservation Of Human Semen, And Subsequent Evaluation Of A Commercially-Available Device To Isolate Motile Sperm, Callum Andrew Robinson

Theses: Doctorates and Masters

The cryopreservation of human semen is a vital asset in assisted reproductive technologies (ART). Although advances have been in the freezing of sperm, further refinement is both necessary and ongoing. Computer-assisted semen analysis (CASA) has been increasingly utilised in both research and diagnostic however there are a range of variables that must first be controlled in order to produce reliable measurements. Following thawing, sperm must be isolated from both the original seminal plasma and the cryoprotectants; the two most used isolation methods include density gradient centrifugation (DGC) and the swim-up method.

The present thesis sought to investigate the following areas …

The Clinical Utility Of The Halosperm Assay And The Development Of A Simplified Method Of Human Semen Storage For The Testing Of Sperm Dna Fragmentation, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Male infertility is typically diagnosed upon routine semen analysis following the World Health Organisation’s (WHO) semen analysis manual. Recent editions of the manual have essentially changed the diagnosis of a semen sample, prompting debate between experts as to which edition should be followed. Deoxyribonucleic Acid (DNA) integrity analysis is proving to be a useful adjunct to semen analysis as 15% of infertile men have a normal semen analysis but they have an increased DNA fragmentation level (DFL) which has been associated with increased disease incidence in any resultant offspring. However, such tests are not endorsed by the WHO, possibly due …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

Yeast As A Model For Studying Aβ Aggregation, Toxicity And Clearance, Prashant R. Bharadwaj

Theses: Doctorates and Masters

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system, characterised by acute memory loss and behavioural symptoms. The AD brain is characterized by the presence of senile amyloid plaques associated with degenerating neurites and inflammatory processes. The major protein component of these amyloid deposits is the amyloid beta (Aβ) protein. The Aβ protein is a 40 or 42 amino acid cleavage product of APP (Amyloid Precursor Protein) which is produced in low levels in the normal ageing brain. Although senile amyloid plaques is the major pathological hallmark of AD brains, accumulating evidence has been presented to …