Neurobiology of tau protein: regulation and deregulation in vivo
Alzheimer’s disease (AD) is the leading form of dementia. The neuropathological hallmarks of Alzheimer’s disease include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP), and neurofibrillary tangles (NFT) of hyperphosphorylated tau protein assembled in paired helical filaments (PHF). NFT pathology is important, since it correlates with the degree of cognitive impairment in AD. Our laboratory focuses on understanding the causes and consequences of tau pathology.
We focus on 3 main research directions, performed mainly in vivo, with the help of transgenic mouse models of AD:
Molecular basis of tau regulation in vivo
Hyperphosphorylation of tau by deregulation of kinases and/or phosphatases has been proposed to dissociate tau from microtubules (MTs), thereby destabilizing the MTs and disrupting MT dependent axonal transport. Thus, we are studying the regulation of tau phosphorylation, tau splicing, and of tau toxicity and aggregation.
Impact of biological and environmental factors on AD pathogenesis
Only a small proportion of AD is due to genetic variants, the large majority of cases (~95%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Here, we study the impact of genetic and biological susceptibilities such as aging, diabetes, inflammation, and external factors, such as anesthesia and trauma, on the development of tau pathology.
Pharmacological treatments of AD pathology
Targeting tauopathy with pharmacological compounds to alleviate the symptoms of AD is a growing field of research. We have been conducting research studying the impact of kinase inhibitors, as well as MT stabilizing drugs on tau pathology in vivo. We have now developed collaborations to study the effects of new compounds, and new therapeutic approaches.
All our research would not be possible without the support and generosity of the Alzheimer’s Society of Canada, the CIHR, the NSERC, the FRSQ, the RQRV, and AFIRMAQ.
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Circadian and sleep/wake-dependent variations in tau phosphorylation are driven by temperature.Journal Article
Sleep, 43 (4), 2020, ISSN: 0161-8105.
The toxin MPTP generates similar cognitive and locomotor deficits in hTau and tau knock-out mice.Journal Article
Brain Res, 1711 , pp. 106-114, 2019, ISSN: 0006-8993.
Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits.Journal Article
J Am Heart Assoc, 8 (9), pp. e011630, 2019, ISSN: 2047-9980.
Administration of the benzodiazepine midazolam increases tau phosphorylation in the mouse brain.Journal Article
Neurobiol Aging, 75 , pp. 11-24, 2019, ISSN: 0197-4580.
Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced tau phosphorylation.Journal Article
Mol Metab, 22 , pp. 110-120, 2019, ISSN: 2212-8778.
Co-occurrence of mixed proteinopathies in late-stage Huntington's disease.Journal Article
Acta Neuropathol, 135 (2), pp. 249-265, 2018, ISSN: 0001-6322.
Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons.Journal Article
Front Mol Neurosci, 11 , pp. 293, 2018.
Corrigendum: Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons.Journal Article
Front Mol Neurosci, 11 , pp. 390, 2018.
Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease.Journal Article
Brain, 140 (11), pp. 2982-2992, 2017, ISSN: 0006-8950.
Differential effects of voluntary treadmill exercise and caloric restriction on tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology fed with Western diet.Journal Article
Prog Neuropsychopharmacol Biol Psychiatry, 79 (Pt B), pp. 452-461, 2017, ISSN: 0278-5846.
- Centre de recherche du CHU de Québec - Université Laval, Subvention, Centre hospitalier universitaire de Québec - Université Laval, Centres de recherche affiliés, from 2017-01-01 to 2099-12-31
- Centre thématique de recherche en neurosciences, Subvention, Institutionnel - BDR, BDR - Centres de recherche reconnus, from 1999-06-01 to 2023-05-01
- Neurobiologie de la protéine tau: régulation et dérégulation in vivo, Subvention, Fonds de recherche du Québec - Santé, Chercheur-boursier Juniors 1 et 2, Seniors, from 2018-07-01 to 2022-06-30
- Regulation of tau phosphorylation and splicing during post-embryonic development., Subvention, Conseil de recherches en sciences naturelles et génie Canada, Subventions à la découverte SD (individuelles et d'équipe), from 2016-04-01 to 2021-03-31
- Untangling tau contribution to cognitive impairments in Huntington’s disease., Subvention, Instituts de recherche en santé du Canada, Subvention Projet, from 2019-04-01 to 2024-03-31
Recently finished projects
- 3rd Neuroforum of the CHU de Québec - Université Laval Research Center: A seminar series of le2aders in neuroscience, Subvention, Instituts de recherche en santé du Canada, Subvention de planification et dissémination, from 2020-01-01 to 2020-03-31
- Targeting tau pathology by modulating temperature, Subvention, Société Alzheimer du Canada, from 2018-07-01 to 2020-06-30