A5068260426- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Functional Brain Connectivity Studies
- Advanced Neuroimaging Techniques and Applications
- Tryptophan and brain disorders
- Advanced MRI Techniques and Applications
- Medical Imaging Techniques and Applications
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disorders and Treatments
- Ultrasound and Hyperthermia Applications
- Lanthanide and Transition Metal Complexes
- Brain Tumor Detection and Classification
- Health Systems, Economic Evaluations, Quality of Life
- Radiopharmaceutical Chemistry and Applications
- Computational Drug Discovery Methods
- Traumatic Brain Injury and Neurovascular Disturbances
- Bone and Joint Diseases
- Neuropeptides and Animal Physiology
- Neurological diseases and metabolism
- Hereditary Neurological Disorders
- Advanced Technologies in Various Fields
- Lysosomal Storage Disorders Research
- Cholinesterase and Neurodegenerative Diseases
University of Toronto
2021-2025
Sunnybrook Health Science Centre
2021-2025
Sunnybrook Hospital
2023-2024
Sunnybrook Research Institute
2021-2024
Ontario Brain Institute
2024
Health Sciences Centre
2022-2023
Landscape Research Group
2023
Authorised Association Consortium
2023
McGill University
2020-2022
Douglas Mental Health University Institute
2022
Disease-modifying treatment trials are increasingly advanced to the prodromal or preclinical phase of Alzheimer's disease (AD), and inclusion criteria based on biomarkers rather than clinical symptoms. Therefore, it is great interest determine which should be combined accurately predict conversion from mild cognitive impairment (MCI) AD dementia. However, up date, only few studies performed a complete A/T/N subject characterization using each CSF imaging markers, they investigated long-term...
GBA1 mutation is the most common genetic risk factor for Parkinson's disease (PD). Replacement of lysosomal enzyme glucocerebrosidase (GCase) slows neurodegeneration in PD models and may be a promising disease-modifying therapy patients with PD. However, recombinant GCase has limited penetration through blood-brain barrier (BBB). Microbubble-mediated magnetic resonance-guided focused ultrasound (MRgFUS) can reversibly disrupt BBB drug delivery.This open-label phase I study investigated...
Abstract The blood–brain barrier (BBB) protects the brain but is also an important obstacle for effective delivery of therapeutics in Alzheimer’s disease and other neurodegenerative disorders. Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to reversibly disrupt BBB. However, treatment diffuse regions across along with effect on relevant pathology need be better characterized. This study open-labelled single-arm trial (NCT03739905) investigate feasibility...
The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity TSPO to identify brain processes appears vary greatly across disorders, disease stages, applied quantification methods. To advance potential biomarker evaluate inflammation anti-inflammatory therapies, better understanding its applicability disorders needed. We...
Background: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid- (A) increases when CSF A 1-42 /A 1-40 ratio is used as compared to levels alone.Objective: In order test this hypothesis, we set up a prospective longitudinal study comparing different amyloid biomarkers for Alzheimer's disease (AD) in clinical setting.Methods: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n 48), cognitively healthy controls 13))...
Abstract INTRODUCTION Hypertension and diabetes are common cardiovascular risk factors that increase Alzheimer's disease (AD) risk. However, it is unclear whether AD differs in hypertensive individuals with without diabetes. METHODS Cognitively normal ( N = 11,074) from the National Coordinating Center (NACC) were categorized as having (1) hypertension (HTN+/DM+), (2) (HTN+/DM‐), or (3) neither (HTN‐/DM‐). HTN+/DM+ HTN+/DM‐ was compared to HTN‐/DM‐. This then investigated those...
Abstract Alzheimer’s disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that distribution tau reactive microglia humans follows spatial patterns variation, so-called gradients organization. Notably, less distinct (“gradient contraction”) are associated with decline regions greater tau, suggesting...
Activated microglia express the translocator protein (TSPO) on outer mitochondrial membrane. <sup>18</sup>F-PBR111 is a second-generation PET ligand that specifically binds TSPO, allowing in vivo visualization and quantification of neuroinflammation. The aim this study was to evaluate whether test–retest variability healthy controls acceptable detect psychosis-associated neuroinflammatory signal schizophrenia. <b>Methods:</b> Dynamic 90-min scans were obtained 17 male (HCs) 11 schizophrenia...
Abstract Introduction Dual‐biomarker positron emission tomography (PET), providing complementary information on cerebral blood flow and amyloid‐β deposition, is of clinical interest for Alzheimer's disease (AD). The purpose this study was to validate the perfusion components early‐phase 18 F‐florbetapir (eAV45), F‐AV45 delivery rate (R1), F‐FDG against 15 O‐H 2 O PET assess how they change with severity. Methods This included ten controls, 19 amnestic mild cognitive impairment, 10 AD...
Abstract It remains unclear to what extent cerebrovascular burden relates amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel Alzheimer's (AD) pathology. In 120 subjects, we investigated the association of vascular (white matter hyperintensity [WMH] volumes) cognition. Using mediation analyses, tested indirect effects WMH on cognition via Aβ deposition ( 18 F‐AV45 positron emission tomography [PET]) neurodegeneration...
Increased brain uptake of <sup>18</sup>F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) widely used quantification, but subject to variability based on choice reference region and changes in cerebral blood flow. Here we validate the SUVR method against gold standard volume distribution (V<sub>T</sub>) assess cross-sectional differences plaque load. <b>Methods:</b> Dynamic 60-min (291 ± 67 MBq) 1-min <sup>15</sup>O-H<sub>2</sub>O (370 scans were...
Abnormal mitochondrial metabolism has been described in the Alzheimer's disease (AD) brain. However, relationship between AD pathophysiology and key processes remains elusive. The purpose of this study was to investigate whether complex I dysfunction is associated with amyloid aggregation or glucose brain atrophy patients mild using positron emission tomography (PET).Amyloid- tau-positive symptomatic clinical dementia rating 0.5 1 (N = 30; mean age ± standard deviation: 71.8 7.6 years)...
Abstract Introduction The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various CNS disorders, but its usefulness appears to vary greatly across disease stages, and applied quantification methods. To advance TSPO potential biomarker evaluate brain inflammation anti-inflammatory therapies, better understanding applicability disorders needed. We conducted transdiagnostic systematic review meta-analysis all vivo...
Inter-individual variability in tau topography challenges the propagation hypothesis of aggregates. To address this gap, we propose Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by spatial continuity stage regions. Longitudinal and cross-sectional MCA large aging cohort identified individual (N = 753) expressing load entorhinal, limbic neocortical Using these profiles, found neuropsychological blood-based milestones early late disease stages. Finally,...
Abstract Background Compelling experimental evidence suggests that microglial activation is involved in the spread of tau neurofibrillary tangles over neocortex Alzheimer’s disease (AD). Here, we tested hypothesis spatial propagation and accumulation colocalize a Braak‐like pattern human brain. Method We studied 130 subjects (86 cognitively unimpaired 44 impairment elderly) with microglia [ 11 C]PBR28 PET, Amyloid 18 F]NAV4694 cognitive tests, magnetic resonance imaging, cerebrospinal fluid...
White matter (WM) injury is frequently observed along with dementia. Positron emission tomography amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little understood about the origin of altered Aβ-PET signal in regions. Here, we investigated relative contributions diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to cognition. We included a unique cohort 115 participants covering spectrum low-to-severe white...
Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent on the pattern hippocampal atrophy, a key substrate memory impacted early extensively in dementia, remains poorly understood.
Background Increased brain uptake on [18F]AV45 PET is a biomarker for Alzheimer’s disease (AD). The standardised value ratio (SUVR) widely used quantification but subject to variability. Here we evaluate how SUVR of cortical target region affected by blood flow changes in the and two frequently reference regions. Methods Regional baseline time-activity curves (TACs) were simulated based metabolite-corrected plasma input functions pharmacokinetic parameters obtained from our previously...
In vivo biomarker abnormalities provide measures to monitor therapeutic interventions targeting amyloid-β pathology as well its effects on downstream processes associated with Alzheimer’s disease pathophysiology. Here, we applied an in longitudinal study design combined imaging and cerebrospinal fluid biomarkers, mirroring those used human clinical trials assess the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment McGill-R-Thy1-APP transgenic rat model. The...
Abstract INTRODUCTION We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS A mediation analysis was performed to assess relationship between neuroimaging markers biomarkers sEF 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or...