Neurobiologie de la protéine tau: régulation et dérégulation in vivo


Emmanuel Planel

Centre hospitalier de l'Université de Québec [CHUQ]


Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

Alzheimer's disease (AD) is the leading form of dementia. There is actually no cure for Alzheimer's disease, but even a treatment that would slow down the progression of the disease by 5 or 10 years will have a tremendous socio-economic impact for Canada. The neuropathological hallmarks of Alzheimer's disease include senile plaques of beta-amyloid (Abeta) peptides (a cleavage product of the Amyloid Precursor Protein, or APP), neurofibrillary tangles (NFT) of hyperphosphorylated tau protein assembled in paired helical filaments (PHF), astrocytes gliosis, and a reduction of the number of neurons and synapses in many areas of the brain. NFT pathology is important since it correlates with the degree of cognitive impairment in AD. 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. Recent preclinical studies have provided strong evidence that general anesthetics may be such an external factor and do exacerbate the neuropathogenesis of AD. Moreover, many clinical studies have shown that anesthesia/surgery can result in post-operative cognitive dysfunction. In this context, understanding the effects of anesthesia and/or surgery on AD pathogenesis is important.

The overall goal of this project is therefore to clarify the impact of different anesthetics during aging, of their method of administration, and of the surgical procedure in normal and transgenic mice models of Alzheimer's disease.