In-vivo synaptic correlates of cognitive reserve
Given that the incidence of Alzheimer’s disease increases with age, it has been estimated that delaying dementia onset by 5 years would decrease the prevalence of late-onset dementia by 50%. In this project we will investigate the biological basis of Cognitive Reserve, a protective property of the brain known to delay dementia onset, but whose underlying mechanisms remain a mystery. Because the cognitive deficits in Alzheimer’s disease are strongly associated with a loss of synapses – the point of communications between neurons – we believe that Cognitive Reserve is first implemented at the synaptic level as a way to preserve neuronal communication. In this project we will take a state-of-the-art microscopy approach to directly visualise the loss of synapses inside the brain of a living Alzheimer’s disease animal model and the compensatory and regenerative events that follows that might serve as the basis of Cognitive Reserve. Given that therapeutics targeting the formation of amyloid pathology have failed in numerous clinical trials, we will focus on the protective mechanisms of the brain to cope with pathology rather than on those leading to pathology in the first place. The outcomes of this project may be instrumental in developing effective therapeutics harnessing these protective mechanisms as a way to delay the onset of dementia.