L'effet neurotoxique des oligomères amyloïde-bêta sur les troubles de la mémoire et du sommeil dans la maladie d'Alzheimer

 

Jonathan Brouillette

Centre de recherche de l'Hôpital du Sacré-Coeur de Montréal

 

Domaine : vieillissement

Programme Chercheurs-boursiers - Junior 1

Concours 2016-2017

Alzheimer's disease (AD) is an age-related neurodegenerative illness that primarily impairs memory in association with sleep loss. Recent studies have shown that soluble amyloid-beta (Abeta) oligomers induce cell death and memory deficits in early AD. However, we still ignore how Abeta oligomers and sleep loss interact together to produce neuronal death and cognitive decline at the onset of AD.

The main objective of this study is to uncover the deleterious impact of Abeta oligomers on memory and sleep hallmarks affected in early AD. To achieve our goal, we will take advantage of our novel AD animal model in which repeated Abeta oligomers injections mimic cell death and cognitive deficits observed in early AD. Electroencephalographic (EEG) measurements will be done to determine sleep alterations in our AD model. We will investigate the role of sleep as an early biomarker of AD and determines the molecular mechanisms underpinning the memory deficits produced by Abeta oligomers within three specific objectives:

Objective 1: Study the role of Abeta oligomers on the acquisition, consolidation and retrieval phases of memory in normal sleep condition, and identify the molecular and sleep modifications sustaining the toxic effect of Abeta oligomers.

Objective 2: Determine to what extent sleep deprivation aggravates the neurotoxic effect of soluble Abeta oligomers, and amplifies memory and sleep disturbances in our AD model.

Objective 3: Evaluate if treatment with transthyretin (the major Abeta binding protein) increases brain clearance of Abeta oligomers, and acts as a novel therapeutic strategy to prevent the adverse effect of Abeta oligomers.

Identifying the specific signature of Abeta oligomers on the different sleep features might serve as a non-invasive biomarker of early AD. A better understanding of the molecules affected by Abeta oligomers will bring essential information to develop new disease modifying therapies efficient at the onset of the illness.