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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Petry S, Nateghi B, Keraudren R, Sergeant N, Planel E, Hébert SS, St-Amour I

Differential Regulation of Tau Exon 2 and 10 Isoforms in Huntington's Disease Brain

Journal Article

Neuroscience, 2022.

Abstract | Links:

Zussy C, John R, Urgin T, Otaegui L, Vigor C, Acar N, Canet G, Vitalis M, Morin F, Planel E, Oger C, Durand T, Rajshree SL, Givalois L, Devarajan PV, Desrumaux C

Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease

Journal Article

Antioxidants (Basel), 11 (5), 2022.

Abstract | Links:

Guisle I, Canet G, Pétry S, Fereydouni-Forouzandeh P, Morin F, Kérauden R, Whittington RA, Calon F, Hébert SS, Planel E

Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia

Journal Article

Neurobiol Aging, 113 , 2022.

Abstract | Links:

Canet G, Zub E, Zussy C, Hernandez C, Blaquiere M, Garcia V, Vitalis M, deBock F, Moreno-Montano M, Audinat E, Desrumaux C, Planel E, Givalois L, Marchi N

Seizure activity triggers tau hyperphosphorylation and amyloidogenic pathways

Journal Article

Epilepsia, 63 (4), 2022.

Abstract | Links:

Alpaugh M, Masnata M, de Rus Jacquet A, Lepinay E, Denis HL, Saint-Pierre M, Davies P, Planel E, Cicchetti F

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

Journal Article

Mol Ther, 30 (4), 2022.

Abstract | Links:

Tournissac M, Vu TM, Vrabic N, Hozer C, Tremblay C, Mélançon K, Planel E, Pifferi F, Calon F

Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model

Journal Article

Alzheimers Res Ther, 13 (1), 2021.

Abstract | Links:

Tournissac M, Leclerc M, Valentin-Escalera J, Vandal M, Bosoi CR, Planel E, Calon F

Metabolic determinants of Alzheimer's disease: A focus on thermoregulation

Journal Article

Ageing Res Rev, 72 , 2021.

Abstract | Links:

Boscher E, Goupil C, Petry S, Keraudren R, Loiselle A, Planel E, Hébert SS

MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice

Journal Article

Front Neurosci, 14 , 2020.

Abstract | Links:

Boscher E, Hernandez-Rapp J, Petry S, Keraudren R, Rainone S, Loiselle A, Goupil C, Turgeon A, St-Amour I, Planel E, Hebert SS

Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212

Journal Article

Front Neurol, 11 , 2020.

Abstract | Links:

Guisle I, Gratuze M, Petry S, Morin F, Keraudren R, Whittington RA, Hebert SS, Mongrain V, Planel E

Circadian and sleep/wake-dependent variations in tau phosphorylation are driven by temperature

Journal Article

Sleep, 43 (4), 2020.

Abstract | Links:

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Active projects

  • Mechanisms of neuronal and vascular impairments in ischemic retinopathies, from 2019-04-01 to 2024-03-31
  • Targeting tau pathology by modulating temperature, from 2018-07-01 to 2022-09-30
  • Untangling tau contribution to cognitive impairments in Huntington’s disease., from 2019-04-01 to 2024-03-31

Recently finished projects

  • Neurobiologie de la protéine tau: régulation et dérégulation in vivo, from 2018-07-01 to 2022-06-30
  • Regulation of tau phosphorylation and splicing during post-embryonic development., from 2016-04-01 to 2022-03-31
Data provided by the Université Laval research projects registery