A5034862340- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Medical Imaging Techniques and Applications
- Functional Brain Connectivity Studies
- Neuroscience and Neuropharmacology Research
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Lanthanide and Transition Metal Complexes
- Receptor Mechanisms and Signaling
- Neurological Disease Mechanisms and Treatments
- Epilepsy research and treatment
- Magnetism in coordination complexes
- Crystallography and molecular interactions
- S100 Proteins and Annexins
- Metal complexes synthesis and properties
- Computational Drug Discovery Methods
- Tryptophan and brain disorders
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Amino Acid Enzymes and Metabolism
- Inorganic and Organometallic Chemistry
- Amyloidosis: Diagnosis, Treatment, Outcomes
Montreal Neurological Institute and Hospital
2015-2025
McGill University
2015-2025
McMaster University
2024
McGill Genome Centre
2017-2023
Douglas Mental Health University Institute
2017-2022
University of Pittsburgh
2022
McGill University Health Centre
2022
Hamamatsu University School of Medicine
2020
National Neuroscience Institute
2017
Université du Québec à Montréal
2000-2010
18F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, levels of retention in brain regions thought contain negligible concentrations PHF raise questions about the interpretation positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested effects MAO-B inhibition on uptake using PET autoradiography. Eight participants...
Braak stages of tau neurofibrillary tangle accumulation have been incorporated in the criteria for neuropathological diagnosis Alzheimer's disease. It is expected that staging using brain imaging can stratify living individuals according to their individual patterns deposition, which may prove crucial clinical trials and practice. However, previous studies first-generation PET agents shown a low sensitivity detect pathology areas corresponding early histopathological (∼20% cognitively...
<h3>Importance</h3> Apolipoprotein E ε4 (<i>APOEε4</i>) is the single most important genetic risk factor for Alzheimer disease. While<i>APOEε4</i>is associated with increased amyloid-β burden, its association cerebral tau pathology has been controversial. <h3>Objective</h3> To determine whether<i>APOEε4</i>is medial temporal independently of amyloid-β, sex, clinical status, and age. <h3>Design, Setting, Participants</h3> This a study 2 cross-sectional cohorts volunteers who were cognitively...
Abstract Gold-standard diagnosis of Alzheimer’s disease (AD) relies on histopathological staging systems. Using the topographical information from [ 18 F]MK6240 tau positron-emission tomography (PET), we applied Braak system to 324 living individuals. We used PET-based stage model trajectories amyloid-β, phosphorylated (pTau) in cerebrospinal fluid (pTau 181 , pTau 217 231 and 235 ) plasma ), neurodegeneration cognitive symptoms. identified nonlinear AD biomarker corresponding spatial extent...
Abstract Background Antibody-based immunoassays have enabled quantification of very low concentrations phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding the diagnosis AD. Mass spectrometry enables absolute multiple p-tau variants within a single run. The goal this study was to compare performance mass assessments 181 , 217 and 231 with established immunoassay techniques. Methods We measured CSF from 173 participants TRIAD cohort 394 BioFINDER-2 using both methods....
Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging Alzheimer's disease (AD). The aim present study was to examine in vitro properties as well vivo kinetics, using gold standard methods, novel positron emission tomography (PET) imaging agent [18F]MK-6240.In [18F]MK-6240 were estimated with autoradiography postmortem brain tissues 14 subjects (seven AD patients and seven age-matched controls). In quantification binding performed 16 (four...
Abstract Introduction Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine associations between MBI and Alzheimer's disease (AD) biomarkers asymptomatic individuals. Methods Ninety‐six cognitively normal individuals underwent MRI, [ 18 F]AZD4694 β‐amyloid‐PET, F]MK6240 tau‐PET. was assessed using Checklist (MBI‐C). Pearson's correlations voxel‐based regressions were used to evaluate relationship MBI‐C score...
Amyloid-β deposition into plaques is a pathologic hallmark of Alzheimer disease appearing years before the onset symptoms. Although cerebral amyloid-β occurs on continuum, dichotomization positive and negative groups has advantages for diagnosis, clinical management, population enrichment trials. <sup>18</sup>F-AZD4694 (also known as <sup>18</sup>F-NAV4694) an imaging ligand with high affinity plaques. Despite being used in multiple academic centers, no studies have assessed quantitative...
Tracking longitudinal tau tangles accumulation across the Alzheimer's disease continuum is crucial to better understand natural history of pathology and for clinical trials. Although available first-generation PET tracers detect in symptomatic individuals, their nanomolar affinity offers limited sensitivity early asymptomatic subjects. Here, we hypothesized novel subnanomolar tracer 18F-MK-6240 can We studied 125 living individuals (65 cognitively unimpaired elderly amyloid-β-negative, 22...
APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and associated with cerebral amyloid-β. However, association between tau pathology, other major proteinopathy of disease, has been controversial. Here, we sought to determine whether relationship pathology determined by local interactions We examined three independent samples cognitively unimpaired, mild cognitive impairment subjects: (1) 211 participants who underwent tau-PET [18F]MK6240 amyloid-PET...
To assess the frequency of biologically defined Alzheimer disease (AD) in relation to age, sex, APOE ε4, and clinical diagnosis a prospective cohort study evaluated with amyloid-PET tau-PET.We assessed cognitively unimpaired (CU) elderly (n = 166), patients amnestic mild cognitive impairment 77), probable AD dementia 62) who underwent evaluation by specialists neuropsychologists addition [18F]AZD4694 tau-PET [18F]MK6240. Individuals were grouped according their biomarker profile. Positive...
Alzheimer’s disease (AD) phenotypes might result from differences in selective vulnerability. Evidence preclinical models suggests that tau pathology has cell-to-cell propagation properties. Therefore, here, we tested the framework amnestic, visuospatial, language, and behavioral/dysexecutive of AD. We report each AD phenotype is associated with a distinct network-specific pattern aggregation, where aggregation concentrated brain network hubs. In all phenotypes, regional load could be...
We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers.
Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography cryo-EM, we identified AD brain tissue with elevated tau burden, purified filaments, determined the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound a 1:1 ratio within cleft paired-helical filament (PHF), engaging glutamine 351, lysine K353, isoleucine 360. This information elucidates basis in quantifying PHF deposits...
<h3>Objective</h3> To determine the associations between amyloid-PET, tau-PET, and atrophy with behavioral/dysexecutive presentation of Alzheimer disease (AD), how these differ from amnestic AD, they correlate to clinical symptoms. <h3>Methods</h3> We assessed 15 patients AD recruited a tertiary care memory clinic, all whom had biologically defined AD. They were compared 25 severity– age-matched group 131 cognitively unimpaired (CU) elderly individuals. All participants evaluated amyloid-PET...
Abstract Alzheimer’s disease (AD) is characterized by the brain accumulation of amyloid-β and tau proteins. A growing body literature suggests that epigenetic dysregulations play a role in interplay hallmark proteinopathies with neurodegeneration cognitive impairment. Here, we aim to characterize an dysregulation associated deposition Using positron emission tomography (PET) tracers selective for amyloid-β, tau, class I histone deacetylase (HDAC isoforms 1–3), find HDAC levels are reduced...
The primary objective of this study was to verify the suitability reference tissue-based quantification methods metabotropic glutamate receptor type 5 (mGluR(5)) with [(11)C]ABP688. This presents in vivo (Positron Emission Tomography (PET)) and vitro (autoradiography) measurements mGluR(5) densities same rats evaluates both noninvasive blood-dependent pharmacokinetic models for [(11)C]ABP688 binding. Eleven underwent PET scans. In five animals, baseline scans were compared blockade...
Abstract Neurofilament light chain (NFL) measurement has been gaining strong support as a clinically useful neuronal injury biomarker for various neurodegenerative conditions. However, in Alzheimer’s disease (AD), its reflection on regional the context of amyloid pathology remains unclear. This study included 83 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 73 AD subjects who were further classified based amyloid-beta (Aβ) status positive or negative (Aβ+ vs Aβ−). In...
Our objective was to evaluate the in vitro binding properties of [
<title>Abstract</title> Tau pathology spreads and accumulates during Alzheimer’s disease (AD), but the relationship between these processes throughout progression remains unclear. We assessed spatiotemporal dynamics of tau spreading accumulation using tau-PET data from 1,175 participants in TRIAD ADNI cohorts, including 277 with 2-year follow-ups. standardized uptake value ratios (SUVR) indexed load, while spatial extent tauopathy (SEOT; proportion abnormal voxels) measured spread....