A5013816751- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Neuroscience and Neuropharmacology Research
- Neurological diseases and metabolism
- Neurological Disease Mechanisms and Treatments
- RNA regulation and disease
- Dementia and Cognitive Impairment Research
- Metabolomics and Mass Spectrometry Studies
- Peroxisome Proliferator-Activated Receptors
- Neurogenesis and neuroplasticity mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Alcohol Consumption and Health Effects
- Genetic Neurodegenerative Diseases
- Single-cell and spatial transcriptomics
- Cholinesterase and Neurodegenerative Diseases
- GDF15 and Related Biomarkers
- Alcoholism and Thiamine Deficiency
- Mass Spectrometry Techniques and Applications
- Epigenetics and DNA Methylation
- Neurological disorders and treatments
- Pluripotent Stem Cells Research
- Advanced Neuroimaging Techniques and Applications
- Global Public Health Policies and Epidemiology
The University of Sydney
2016-2025
Cooperative Trials Group for Neuro-Oncology
2023-2024
University of Wollongong
2022
Graz University of Technology
2022
UNSW Sydney
2007-2022
Harry Perkins Institute of Medical Research
2021
Fujitsu (United States)
2019
Conference Board of Canada
2017-2019
University of Birmingham
2015
Neurology, Inc
2015
Amyloid-β (Aβ) toxicity in Alzheimer's disease (AD) is considered to be mediated by phosphorylated tau protein. In contrast, we found that, at least early disease, site-specific phosphorylation of inhibited Aβ toxicity. This specific was the neuronal p38 mitogen-activated protein kinase p38γ and interfered with postsynaptic excitotoxic signaling complexes engaged Aβ. Accordingly, depletion exacerbated circuit aberrations, cognitive deficits, premature lethality a mouse model AD, whereas...
Neurogenesis in the postnatal human brain occurs two neurogenic niches; subventricular zone (SVZ) wall of lateral ventricles and subgranular (SGZ) hippocampus. The extent to which this physiological process continues into adulthood is an area ongoing research. This study aimed characterize markers cell proliferation assess efficacy antibodies used identify neurogenesis both niches brain.
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, cell-specific effect these is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from parietal cortex AD autosomal dominant (APP PSEN1) risk-modifying variant (APOE, TREM2 MS4A) carriers. Within individual cell types, capture commonly dysregulated across groups. specific...
SUMMARY There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities cells required molecular functional analyses. We describe here new model based on from human olfactory mucosa, organ smell, which regenerates throughout life neural stem cells. Olfactory mucosa biopsies were obtained healthy controls patients with either schizophrenia, neurodevelopmental psychiatric disorder, or Parkinson’s disease,...
Background Without appropriate cellular models the etiology of idiopathic Parkinson's disease remains unknown. We recently reported a novel patient-derived model generated from biopsies olfactory mucosa (termed neurosphere-derived (hONS) cells) which express functional and genetic differences in disease-specific manner. Transcriptomic analysis Patient Control hONS cells identified NRF2 transcription factor signalling pathway as most differentially expressed disease. Results tested robustness...
Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of association studies Parkinson disease (PD) based on populations Caucasian descent. The extent to which these effects are consistent across different is unknown.Investigators from the Genetic Epidemiology Parkinson's Disease Consortium were invited participate study. A total 11 SNPs genotyped 8,750 cases and 8,955 controls. Fixed as well random models used provide summary risk estimates for variants. We...
The pathogenesis of Alzheimer's disease (AD) remains to be elucidated. Oxidative damage and excessive beta-amyloid oligomers are components progression but it is unclear how these factors temporally related. At post mortem, the superior temporal gyrus (STG) AD cases contains plaques, displays few tangles only moderate neuronal loss. STG at mortem may represent a brain region that in early stages or alternately resistant pathogenesis. We evaluated expression profiles activity endogenous...
Microglial associations with both the major Alzheimer's disease (AD) pathognomonic entities, β-amyloid-positive plaques and tau-positive neurofibrillary tangles, have been noted in previous investigations of human tissue mouse models. However, precise nature their role pathogenesis AD is debated; working hypothesis that pro-inflammatory activities activated microglia contribute to progression. In contrast, others proposed microglial dystrophy a loss physiological neuroprotective promotes...
The study of Parkinson's disease (PD), like other complex neurodegenerative disorders, is limited by access to brain tissue from patients with a confirmed diagnosis. Alternatively the peripheral tissues may offer some insight into molecular basis susceptibility and progression, but this approach still relies on benchmark relevant changes against. Several studies have reported whole-genome expression profiling in post-mortem concordance between these analyses lacking. Here we apply...
Abstract Executive function (EF) is a set of cognitive capabilities considered essential for successful daily living, and negatively affected by ageing neurodegenerative conditions. Underpinning EF performance are functional nodes in the executive control network (ECN), while structural connectivity underlying this not well understood. In paper, we evaluated white matter tracts that interconnect ECN investigated their relationship to performance. Using high‐angular resolution diffusion MRI...
Abstract Tau pathology in Alzheimer’s disease (AD) spreads a predictable pattern that corresponds with symptoms and severity. At post-mortem there are cortical regions range from mildly to severely affected by tau neuronal loss. A comparison of the molecular signatures these differentially areas within cases between controls may allow temporal modelling progression. Here we used RNA sequencing explore differential gene expression primary visual cortex moderately precuneus ten age-, gender-...
Abstract Amyloidogenic processing of the amyloid precursor protein (APP) forms amyloid-β peptide (Aβ) component pathognomonic extracellular plaques AD. Additional early cortical changes in AD include neuroinflammation and elevated iron levels. Activation innate immune system brain is a neuroprotective response to infection; however, persistent linked neuropathology by uncertain mechanisms. Non-parametric machine learning analysis on transcriptomic data from large neuropathologically...
Abstract Background The risk for dementia increases exponentially from the seventh decade of life. Identifying and understanding biochemical changes that sensitize ageing brain to neurodegeneration will provide new opportunities prevention treatment. This study aimed determine how major genetic factors affect hippocampal proteome lipidome neurologically-normal humans over age 65. hippocampus was chosen as it is highly susceptible atrophy with in several neurodegenerative diseases. Methods...
Abstract Highly multiplexed in situ imaging cytometry assays have made it possible to study the spatial organization of numerous cell types simultaneously. We addressed challenge quantifying complex multi‐cellular relationships by proposing a statistical method which clusters local indicators association. Our approach successfully identifies distinct tissue architectures datasets generated from three state‐of‐the‐art high‐parameter demonstrating its value summarizing information‐rich data...
Abstract Background Alcohol use disorder (AUD) is associated with increased mortality and morbidity risk. A reason for this could be accelerated biological aging, which strongly influenced by disease processes such as inflammation. As recent studies of AUD show changes in DNA methylation gene expression neuroinflammation‐related pathways the brain, aging represents a potentially important construct understanding adverse effects substance disorders. Epigenetic clocks have shown blood samples...
Nitrosative stress is a feature of Alzheimer's disease (AD).
The overwhelming majority of dominant mutations causing early onset familial Alzheimer's disease (EOfAD) occur in only three genes, PSEN1, PSEN2, and APP. An effect-in-common these is alteration production the APP-derived peptide, amyloid β (Aβ). It this key fact that underlies authority Amyloid Hypothesis has informed research for over two decades. Any challenge to must offer an alternative explanation relationship between PSEN genes In paper, we explore one possible - dysregulation...