45 results match your criteria: "and Krembil Brain Institute[Affiliation]"
Acta Neuropathol
October 2022
Dementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, 2109, Australia.
In Alzheimer's disease (AD), where amyloid-β (Aβ) and tau deposits in the brain, hyperexcitation of neuronal networks is an underlying disease mechanism, but its cause remains unclear. Here, we used the Collaborative Cross (CC) forward genetics mouse platform to identify modifier genes of neuronal hyperexcitation. We found LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations.
View Article and Find Full Text PDFJ Neurol
October 2022
Tanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, University of Toronto, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 2S8, Canada.
Background: Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration.
Methods: Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included.
Neurology
May 2022
From the Institute of Medical Science, Faculty of Medicine (A.S., C.G., A.F., D.M.A.), and Division of Neurology, Department of Medicine (P.M., A.F., D.M.A.), University of Toronto; Adult Epilepsy Genetics Program, Department of Neurology, Krembil Research Institute (A.S., P.M., Q.Z.A., D.M.A.), and Krembil Brain Institute (C.G., A.F., D.M.A.), University Health Network, and Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic (C.G., A.F.), Toronto Western Hospital; Pediatric Neurology (C.G.), The Hospital for Sick Children, Toronto, Canada; Division of Neurology, Epilepsy Center (A.T.B.), Ann & Robert H. Lurie Children's Hospital of Chicago; and Department of Pediatrics (A.T.B.), Northwestern Feinberg School of Medicine, Chicago, IL.
Background And Objectives: Relative to the pediatric population, there is limited information about Dravet syndrome (DS) in adults. In addition to some of the gait abnormalities reported in children with DS (such as crouch gait and ataxia), adults with this condition have other gait and motor disturbances. Our primary objective was to examine gait and motor manifestations in adults with DS.
View Article and Find Full Text PDFBrain
March 2023
Ontario Forensic Pathology Service, Toronto, Ontario M3M 0B1, Canada.
Nodding syndrome is an enigmatic recurrent epidemic neurologic disease that affects children in East Africa. The illness begins with vertical nodding of the head and can progress to grand mal seizures and death after several years. The most recent outbreak of nodding syndrome occurred in northern Uganda.
View Article and Find Full Text PDFActa Neuropathol Commun
April 2022
Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
Traumatic brain injury (TBI) is associated with the development of a range of neurodegenerative pathologies, including chronic traumatic encephalopathy (CTE). Current consensus diagnostic criteria define the pathognomonic cortical lesion of CTE neuropathologic change (CTE-NC) as a patchy deposition of hyperphosphorylated tau in neurons, with or without glial tau in thorn-shaped astrocytes, typically towards the depths of sulci and clustered around small blood vessels. Nevertheless, although incorporated into consensus diagnostic criteria, the contribution of the individual cellular components to identification of CTE-NC has not been formally evaluated.
View Article and Find Full Text PDFEur J Neurol
August 2022
Edmond J. Safra Program in Parkinson's Disease, Rossy Program for PSP Research and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
Background And Purpose: Progressive supranuclear palsy (PSP) encompasses a broader range of disease courses than previously appreciated. The most frequent clinical presentations of PSP are Richardson syndrome (RS) and PSP with a predominant Parkinsonism phenotype (PSP-P). Time to reach gait dependence and cognitive impairment have been proposed as prognostic disease milestones.
View Article and Find Full Text PDFJ Alzheimers Dis
May 2022
Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada.
Background: Down syndrome (DS) is frequently associated with Alzheimer's disease (AD)-related neuropathological changes. There are few observations on the spectrum of mixed proteinopathies in DS patients.
Objective: This study aimed to evaluate multiple disease-associated proteinopathies in a series of DS cases.
Nat Commun
March 2022
Institute for Stroke and Dementia Research, University Hospital of Munich, LMU Munich, Munich, Germany.
Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. Tau is assumed to spread prion-like across connected neurons, but the mechanisms of tau propagation are largely elusive in 4-repeat tauopathies, characterized not only by neuronal but also by astroglial and oligodendroglial tau accumulation. Here, we assess whether connectivity is associated with 4R-tau deposition patterns by combining resting-state fMRI connectomics with both 2 generation F-PI-2620 tau-PET in 46 patients with clinically diagnosed 4-repeat tauopathies and post-mortem cell-type-specific regional tau assessments from two independent progressive supranuclear palsy patient samples (n = 97 and n = 96).
View Article and Find Full Text PDFClin Neurophysiol
November 2021
Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, Toronto, Ontario, Canada.
Objective: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human.
Methods: Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals.
Results: Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers.
Nat Rev Neurol
October 2021
Department of Neurology, Hanover Medical School, Hanover, Germany.
Tauopathies are classified according to whether tau deposits predominantly contain tau isoforms with three or four repeats of the microtubule-binding domain. Those in which four-repeat (4R) tau predominates are known as 4R-tauopathies, and include progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, globular glial tauopathies and conditions associated with specific MAPT mutations. In these diseases, 4R-tau deposits are found in various cell types and anatomical regions of the brain and the conditions share pathological, pathophysiological and clinical characteristics.
View Article and Find Full Text PDFInt J Mol Sci
July 2021
Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology and Rehabilitation Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
The gold standard for classification of neurodegenerative diseases is postmortem histopathology; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia-ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann-Pick disease Type C. Postmortem evaluation unexpectedly demonstrated neurodegeneration with 4-repeat tau deposition in a distribution diagnostic of progressive supranuclear palsy (PSP).
View Article and Find Full Text PDFActa Neuropathol Commun
May 2021
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada.
When injected into genetically modified mice, aggregates of the amyloid-β (Aβ) peptide from the brains of Alzheimer's disease (AD) patients or transgenic AD mouse models seed cerebral Aβ deposition in a prion-like fashion. Within the brain, Aβ exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Aβ variants to the seeding behavior of Aβ aggregates remains unknown. Here, we have investigated the relative seeding activities of Aβ aggregates composed exclusively of recombinant Aβ38, Aβ40, Aβ42, or Aβ43.
View Article and Find Full Text PDFNeurology
June 2021
From the Department of Neurology (J.Y.), Sungkyunkwan University School of Medicine, and Neuroscience Center (J.Y.), Samsung Medical Center, Seoul, Korea; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic (J.Y., G.G.K., A.F.), and Division of Neurosurgery, Department of Surgery (P.K.), Toronto Western Hospital; Division of Neurology (J.Y., G.G.K., A.F.), University of Toronto; and Krembil Brain Institute (G.G.K., A.F.), Toronto, Canada.
Acta Neuropathol Commun
March 2021
Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
Efforts to characterize the late effects of traumatic brain injury (TBI) have been in progress for some time. In recent years much of this activity has been directed towards reporting of chronic traumatic encephalopathy (CTE) in former contact sports athletes and others exposed to repetitive head impacts. However, the association between TBI and dementia risk has long been acknowledged outside of contact sports.
View Article and Find Full Text PDFEur J Neurol
October 2020
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Background And Purpose: Argyrophilic grain disease (AGD) is a limbic-predominant 4R-tauopathy. AGD is thought to be an age-related disorder and is frequently detected as a concomitant pathology with other neurodegenerative conditions. There is a paucity of data on the clinical phenotype of pure AGD.
View Article and Find Full Text PDFActa Neuropathol
August 2020
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains.
View Article and Find Full Text PDFLancet Neurol
May 2020
Department of Neurology, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
World Neurosurg
August 2019
Department of Neurosurgery, La Princesa Hospital, Madrid, Spain.
Background: Diagnostic methods of the epileptogenic area continue to be a challenge in epilepsy surgery research. We hypothesized that temporal lobe epilepsy (TLE) will result in white matter changes that can be detected using diffusion tensor imaging. Measurement of white matter diffusivity will therefore be useful for presurgical assessment.
View Article and Find Full Text PDFNutrients
March 2019
Centre for Mental Health, University Health Network, Network - Toronto General Hospital, 200 Elizabeth Street, 8th Floor, Toronto, ON M5G 2C4, Canada.
The concept of food addiction has generated much controversy. In comparison to research examining the construct of food addiction and its validity, relatively little research has examined the broader implications of food addiction. The purpose of the current scoping review was to examine the potential ethical, stigma, and health policy implications of food addiction.
View Article and Find Full Text PDFClin Neurophysiol
April 2019
Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada. Electronic address:
Deep brain stimulation (DBS) implanted in different basal ganglia nuclei regulates the dysfunctional neuronal circuits and improves symptoms in movement disorders. However, the understanding of the neurophysiological mechanism of DBS is at an early stage. Transcranial magnetic stimulation (TMS) can be used safely in movement disorder patients with DBS, and can shed light on how DBS works.
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