Alzheimer disease (AD) is the most prevalent form of dementia in the elderly. Vascular pathology is central in AD pathogenesis although the mechanisms underlying the vascular defects continue to elude us . CD2-associated protein (CD2AP) is linked to AD by genetic studies (it is a top 10 AD predisposition factor) and post-mortem data. This protein is super enriched in brain capillary endothelial cells forming the blood-brain barrier but its roles in this specialized cell type is undefined. Using a multidisciplinary approach that encompasses genetically modified mice lacking CD2AP in the brain endothelium, two-photon microscopy and human AD samples from the RUSH cohort, my team has identified key roles for CD2AP in brain vascular functions (neurovascular coupling, cerebral blood flow regulation). We went on to identify a novel molecular pathway centred on CD2AP that promote brain blood  vessels dilation and could be harnessed to treat cerebrovascular dysfunction in AD. Furthermore, CD2AP modulates this pathway in a sex-dependent manner suggesting the possibility for sex-dependent therapies. This work is published in the prestigious journal Neuron (Vandal et al., Loss of endothelial CD2AP causes sex-dependent cerebrovascular dysfunction, in press).

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