William S. Brooks
A5045052392- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Neurological diseases and metabolism
- Functional Brain Connectivity Studies
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Bioinformatics and Genomic Networks
- Liver Disease and Transplantation
- Prion Diseases and Protein Misfolding
- Health Systems, Economic Evaluations, Quality of Life
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Advanced Neuroimaging Techniques and Applications
- Computational Drug Discovery Methods
- Statistical Methods in Clinical Trials
- Nuclear Receptors and Signaling
- Chronic Disease Management Strategies
- Hereditary Neurological Disorders
- RNA Research and Splicing
- S100 Proteins and Annexins
- Liver Disease Diagnosis and Treatment
- 14-3-3 protein interactions
- Pharmacological Receptor Mechanisms and Effects
Neuroscience Research Australia
2015-2025
UNSW Sydney
2014-2025
Alzheimer’s Disease Neuroimaging Initiative
2023
Union Bank of Switzerland
2023
Center for Inherited Blood Disorders
2022
Neurology Center of Southern California
2021
Stanford University
2021
Uniformed Services University of the Health Sciences
2021
The Royal Melbourne Hospital
2021
Università di Camerino
2021
Abstract Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of TDP-43 is a major component, characteristic pathological feature most ALS FTD patients. Here we use genome-wide linkage analysis large ALS/FTD kindred to identify novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified CCNF missense mutation...
Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against pathology, its effect on tau pathology and potential beneficial role people with disease still unclear. Our aim was study associations between dynamics soluble TREM2, as a biomarker signalling, amyloid β (Aβ) deposition, tau-related neuroimaging markers, cognitive decline,...
Abstract Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation amyloid-β (Aβ) peptide into plaques and microtubule protein tau neurofibrillary tangles (NFTs)—are hallmarks disease. However, other brain processes are thought to be key mediators Aβ plaque NFT pathology. How these additional pathologies evolve over course is currently unknown. Here we show that proteomic measurements in autosomal dominant AD...
Genetic mutations in the tau gene on chromosome 17 are known to cause frontotemporal dementias. We have identified a novel silent mutation (S305S) subject without significant atrophy or cellular degeneration of frontal and temporal cortices. Rather pathology was characteristic progressive supranuclear palsy, with neurofibrillary tangles concentrating within subcortical regions basal ganglia. Two affected family members presented symptoms dementia later developed neurological deficits...
This paper reports the preliminary results of a prospective randomized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt (DSRS) in management patients with cirrhosis bleeding. Seventy-one have been entered; 36 received 35 DSRS. Randomization study population was stratified on Child's A/B (56%) C (44%). Sixty-one per cent had alcoholic 39% nonalcoholic cirrhosis. No lost to follow-up, which currently stands at median 26 months. Rebleeding occurred significantly (p <...
Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia. Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused sarcoma (FUS) protein. Our objective was to identify causative gene an FTLD-MND pedigree with no mutations known dementia genes.A mutation screen candidate genes, luciferase assays, quantitative polymerase chain reaction...
<h3>Background</h3> Supported by compelling genetic data regarding early-onset familial Alzheimer disease (AD), the amyloid β-peptide (Aβ)–centric theory holds that Aβ is involved in pathogenesis of sporadic AD. Mutations precursor protein (<i>APP</i>), presenilin 1 (<i>PSEN1</i>), and 2 (<i>PSEN2</i>) genes lead to increased levels before symptoms arise. <h3>Objectives</h3> To evaluate pattern Pittsburgh Compound B (PiB) retention subjects with different autosomal dominant mutations...
To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with progranulin (GRN), an important cause frontotemporal lobar degeneration (FTLD).A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases FTLD TAR DNA-binding protein 43-kDa (TDP-43)-positive inclusions (FTLD-TDP). We identified FTLD-TDP pathogenic GRN (GRN+ FTLD-TDP), assessed genetic clinical characteristics, compared them 453 patients...
Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence multiple imaging tracers presents challenges to interpretation such measurements. This study a direct comparison Pittsburgh compound B-based florbetapir-based same participants from two independent cohorts using crossover design.Pittsburgh B florbetapir PET data three different were analyzed previously established pipelines obtain global These measurements...
Abstract Frontotemporal dementia and amyotrophic lateral sclerosis are clinically pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.2 genome-wide significant linkage in large European Australian family autosomal dominant inheritance of frontotemporal no mutation known or genes. Here we demonstrate the segregation novel missense variant CYLD (c.2155A&gt;G, p.M719V) within region as cause this family....
"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted has been well established in symptomatic Alzheimer disease (AD), but is underexplored preclinical AD. Prior studies have typically used structural MRI, resting-state functional connectivity (FC) remains underexplored. Our model predicted from FC 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained 145 amyloid-negative, 151 AD, and 156...
Abstract The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons case–control studies. age onset highly predictable within families, allowing researchers to estimate individual’s point the trajectory. These characteristics allow candidate...
Eleven early-onset dementia families, all with affected individuals who have either presented clinical symptoms of early onset familial Alzheimer's disease (EOFAD) or been confirmed to EOFAD by autopsy, and two cases biopsy-confirmed AD pathology, were screened for missense mutations in the entire coding region presenilin-1 (PS-1) -2 (PS-2) genes. Missense detected direct sequence analysis PCR products amplified from genomic DNA templates individuals. Three pedigrees attributable known PS-1...