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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Winston CN, Noel A, Neustadtl A, Parsadanian M, Barton DJ, Chellappa D, Wilkins TE, Alikhani AD, Zapple DN, Villapol S, Planel E, Burns MP

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.

Journal Article

Am J Pathol, 186 (3), pp. 552-67, 2016, ISSN: 0002-9440.

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Vandal M, White PJ, Tournissac M, Tremblay C, St-Amour I, Drouin-Ouellet J, Bousquet M, Traversy MT, Planel E, Marette A, Calon F

Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease.

Journal Article

Neurobiol Aging, 43 , pp. 47-57, 2016, ISSN: 0197-4580.

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Gratuze M, Julien J, Morin F, Calon F, Hebert SS, Marette A, Planel E

High-fat, high-sugar, and high-cholesterol consumption does not impact tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology.

Journal Article

Neurobiol Aging, 47 , pp. 71-73, 2016, ISSN: 0197-4580.

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Smith PY, Hernandez-Rapp J, Jolivette F, Lecours C, Bisht K, Goupil C, Dorval V, Parsi S, Morin F, Planel E, Bennett DA, Fernandez-Gomez FJ, Sergeant N, Buee L, Tremblay ME, Calon F, Hebert SS

miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo.

Journal Article

Hum Mol Genet, 24 (23), pp. 6721-35, 2015, ISSN: 0964-6906.

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Vandal M, White PJ, Chevrier G, Tremblay C, St-Amour I, Planel E, Marette A, Calon F

Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

Journal Article

FASEB J, 29 (10), pp. 4273-84, 2015, ISSN: 0892-6638.

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Whittington RA, Virag L, Gratuze M, Petry FR, Noel A, Poitras I, Truchetti G, Marcouiller F, Papon MA, El Khoury N, Wong K, Bretteville A, Morin F, Planel E

Dexmedetomidine increases tau phosphorylation under normothermic conditions in vivo and in vitro.

Journal Article

Neurobiol Aging, 36 (8), pp. 2414-28, 2015, ISSN: 0197-4580.

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Noel A, Poitras I, Julien J, Petry FR, Morin F, Charron J, Planel E

ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro.

Journal Article

Neurobiol Aging, 36 (2), pp. 901-2, 2015, ISSN: 0197-4580.

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Gratuze M, Noel A, Julien C, Cisbani G, Milot-Rousseau P, Morin F, Dickler M, Goupil C, Bezeau F, Poitras I, Bissonnette S, Whittington RA, Hebert SS, Cicchetti F, Parker JA, Samadi P, Planel E

Tau hyperphosphorylation and deregulation of calcineurin in mouse models of Huntington's disease.

Journal Article

Hum Mol Genet, 24 (1), pp. 86-99, 2015, ISSN: 0964-6906.

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Hernandez-Rapp J, Smith PY, Filali M, Goupil C, Planel E, Magill ST, Goodman RH, Hebert SS

Memory formation and retention are affected in adult miR-132/212 knockout mice.

Journal Article

Behav Brain Res, 287 , pp. 15-26, 2015, ISSN: 0166-4328.

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Vandal M, White PJ, Tremblay C, St-Amour I, Chevrier G, Emond V, Lefrancois D, Virgili J, Planel E, Giguere Y, Marette A, Calon F

Insulin reverses the high-fat diet-induced increase in brain Aβ and improves memory in an animal model of Alzheimer disease.

Journal Article

Diabetes, 63 (12), pp. 4291-301, 2014, ISSN: 0012-1797.

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72 entries « 3 of 8 »
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Active projects

  • 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
  • Mechanisms of neuronal and vascular impairments in ischemic retinopathies, Subvention, Instituts de recherche en santé du Canada, Subvention Projet, from 2019-04-01 to 2024-03-31
  • 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
Data provided by the Université Laval research projects registery