Project Overview

Alzheimer’s Disease (AD) is the most common cause of dementia, accounting for over two thirds of cases. As of 2013, there are over 44 million people with dementia worldwide. This number is estimated to increase to over 75 million in 2030; 1.4 million of these will be in Canada. Today, the combined medical costs and lost earnings due to dementia accounts for a total of $33 billion per year. With regard to AD, there are currently no successful treatments, making the discovery of effective therapeutic interventions critical. The major hallmark of AD is cognitive impairment linked to neuronal dystrophy, synaptic impairment and finally death of neurons (i.e., neurodegeneration). The brain contains billions of neurons, and substantially more non-neuronal cells called glia; the major ones relevant to this proposal are astrocytes. While most therapeutic approaches target the neurons to prevent their death, this proposal focuses both on neurons and astrocytes to enhance their ability to protect neurons from death. We specifically propose to target a unique set of membrane channels in astrocytes and neurons which modulate the extracellular environment in which the cells of the brain must function. The outcome of these studies will be the identification of unique new drugs which will not only directly target neurons but also enhance the astrocytes’ abilities to protect neurons that are vulnerable to degeneration in AD.