LOU/C/J Rat: An Experimental Model of Cognitive Resilience in the Field of Alzheimer’s Disease

The main goal of our project is to identify and characterize the neuroprotective mechanisms involved in cognitive resilience, i.e. the ability to remain cognitively normal despite significant AD pathology.

To achieve this, we aim to model the cognitive resilience in rodents, by combining a rat model of successful aging (named LOU/c/jall rat) with a recently developed model of the early stages of human Alzheimer’s disease (the AAV-AD rat model; https://www.agent-biotech.com/). We hypothesize that LOU/c/jall rats will be resilient to Alzheimer’s disease pathology and will display lower cognitive impairment than Wistar rats, from which they genetically derive. By examining the cerebral changes involved in such resilience, we expect to gain new insights in the search for therapeutic targets with a particular interest in serotonergic system modulation.

Our project will help to gain a broad scientific understanding on the neuroplasticity processes underlying the cognitive resilience in Alzheimer’s disease mimicking pathology, which is a core research theme still unmet in Alzheimer’s disease. By shedding light on molecular changes involved in resilience, we expect to innovate by testing new therapeutic strategies related to serotonergic receptors modulation to prevent and/or limit the development of Alzheimer’s disease.

The completion of this project will afford a better understanding of the neuroprotective mechanisms underlying the cognitive resilience to Alzheimer’s disease pathology. This project will thus provide multiple new targets of interest that may improve the therapeutics and treatments of Alzheimer’s disease in order to delay the progression of cognitive impairments.