Grant: Project Grant

Alzheimer's disease (AD) and related dementia currently impact more than 747,000 Canadians and over 44 million people worldwide, exerting a tremendous socioeconomic burden on society. A one-year delay in dementia onset could prevent nearly 500,000 cases over three decades, whereas delaying onset by a decade could prevent over 4 million new cases by 2050. Thus, there is an urgent need to develop effective early diagnosis and treatment strategies for AD. Recently, a specific protein called ROCK2 was found to be overexpressed in the brain at the earliest stage of AD, and ROCK2 expression was found to be elevated in postmortem brain tissues of AD patients and in AD mouse models. In addition, medical imaging studies using positron emission tomography (PET) showed that patients with mild cognitive impairment (MCI) and early AD exhibit significant synaptic loss in the brain regions related to memory and learning, and this synaptic loss is expected to be mediated through activation of the rho/ROCK2 signaling pathway. These data demonstrate the potential of detecting preclinical and prodromal AD through ROCK2 PET imaging, which may lead to identification of new therapeutic targets with a defined early intervention time window to delay or prevent the synapse loss and onset of dementia. Therefore, the proposed research will develop and translate ROCK2 PET imaging probes for future clinical investigations. Successful completion of this project will yield a ROCK2 PET imaging probe that is ready to be tested in humans as a sensitive and non-invasive method for early detection of AD, which will allow early interventions to slow and ultimately halt disease progression.