A5062012597- Glioma Diagnosis and Treatment
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Brain Metastases and Treatment
- Meningioma and schwannoma management
- Neurological diseases and metabolism
- Acute Ischemic Stroke Management
- Cerebrovascular and Carotid Artery Diseases
- Cerebrovascular and genetic disorders
- Cancer, Hypoxia, and Metabolism
- Genetic Neurodegenerative Diseases
- Genetic factors in colorectal cancer
- Radiomics and Machine Learning in Medical Imaging
- MRI in cancer diagnosis
- Neurofibromatosis and Schwannoma Cases
- Intracerebral and Subarachnoid Hemorrhage Research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Genetics and Neurodevelopmental Disorders
- Pituitary Gland Disorders and Treatments
- Genomics and Rare Diseases
Health Sciences Centre
2016-2025
Sunnybrook Health Science Centre
2016-2025
University of Toronto
2016-2025
Sunnybrook Research Institute
2021-2024
Sunnybrook Hospital
2021-2024
Deleted Institution
2021-2023
Children's Research Hospital
2023
National Institute of Neurological Disorders and Stroke
2023
St. Jude Children's Research Hospital
2022
Centre National pour la Recherche Scientifique et Technique (CNRST)
2021
Abstract Mutations in proteins like FUS which cause Amyotrophic Lateral Sclerosis (ALS) result the aberrant formation of stress granules while ALS-linked mutations other impede elimination granules. Repeat expansions C9ORF72, major ALS, reduce C9ORF72 levels but how this impacts is uncertain. Here, we demonstrate that associates with autophagy receptor p62 and controls by autophagy. This requires to associate via Tudor protein SMN proteins, including FUS, are symmetrically methylated on...
White matter hyperintensities (WMH) are prevalent. Although arteriolar disease has been implicated in their pathogenesis, venous pathology warrants consideration. We investigated relationships of WMH with histologic venous, and white abnormalities correlated findings premortem neuroimaging. Three regions periventricular were sampled from archived autopsy brains 24 pathologically confirmed Alzheimer (AD) 18 age-matched nonAD patients. Using trichrome staining, collagenosis (VC) veins (<150 µm...
Objective A noncoding hexanucleotide repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). It has been reported that causes a downregulation transcripts, suggesting haploinsufficiency may contribute to disease pathogenesis. Two protein isoforms are generated from three alternatively spliced transcripts ; long form (C9‐L) short (C9‐S), their function(s) largely unknown owing lack specific antibodies. Methods...
Abstract Background Liquid biopsy is promising for early detection, monitoring of response, and recurrence cancer. The blood-brain barrier (BBB) limits the shedding biomarker, such as cell-free DNA (cfDNA), into blood from brain tumors, their detection by conventional assays. Transcranial MR-guided focused ultrasound (MRgFUS) can safely transiently open BBB, providing an opportunity less-invasive access to pathology. We hypothesized that MRgFUS enrich signal circulating brain-derived...
Spine stereotactic radiosurgery (SRS) is increasingly being used to treat metastatic spinal tumors. As the experience matures, high rates of vertebral compression fracture (VCF) are observed. What unknown mechanism action; it has been postulated but not confirmed that radiation itself a contributing factor. This case report describes 2 patients who were treated with spine SRS subsequently developed signal changes on MRI consistent tumor progression and VCF; however, biopsy diagnosis...
The presence of lower molecular weight species comprising the C-terminal region TAR DNA-binding protein 43 (TDP-43) is a characteristic TDP-43 proteinopathy in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here, we have identified novel splice variant that upregulated ALS generates 35-kDa N-terminally truncated through use an alternate translation initiation codon (ATGMet85), denoted here as Met85-TDP-35. Met85-TDP-35 expressed ectopically human...
To determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) dementia with Lewy bodies (DLB).A total of 289 patients (AD = 239; DLB 50) underwent volumetric MRI, neuropsychological testing, genotyping. Total WMH volumes were quantified. Neuropsychological test scores included a confirmatory factor analysis to identify domains encompassing attention/executive functions, learning/memory, language, for each...
Abstract Background We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer’s disease (AD) frontotemporal lobar degeneration (FTLD). Methods Autopsy-confirmed cases were identified from Sunnybrook Dementia Study, including 15 AD 58 FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick’s] 11 Corticobasal Degeneration Progressive Supranuclear Palsy cases). Healthy...
Objective Periventricular white matter hyperintensities (pvWMHs) are commonly observed on MRI in older individuals and associated with cognitive motor decline. The etiology of pvWMH remains unknown. Venous collagenosis has been implicated, which may also interfere perivascular fluid flow leading to dilation spaces (PVS). Here, we examine relationships between vivo volume ex morphological quantification the PVS veins arteries. Methods Brain tissue from 25 Oregon Alzheimer's Disease Research...
BackgroundPick's disease is a rare and predominantly sporadic form of frontotemporal dementia that classified as primary tauopathy. Pick's pathologically defined by the presence in frontal temporal lobes Pick bodies, composed hyperphosphorylated, three-repeat tau protein, encoded MAPT gene. has two distinct haplotypes, H1 H2; haplotype major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy corticobasal degeneration), H2 protective these disorders. The aim...
Abstract Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability hallmark feature of amyotrophic accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive late pre-symptomatic SOD1*G93A mouse model sclerosis. We discovered that using adeno-associated virus-mediated delivery chemogenetic technology...
Amyotrophic lateral sclerosis (ALS) patients, includingC9orf72-carriers and identical twins [1], have highly variable disease characteristics (e.g., duration age/site of onset) [7], suggesting the influence epigenetic variations.DNA methylation (DNAm) is a key modification linked to risk several neurodegenerative diseases (Supplementary introduction).The cumulative assessment DNAm levels at age-related CpGs allows estimation multi-tissue age (epigenetic clock), which could be more accurate...