Grant: Travel Awards - Institute Community Support

Azheimer's Disease (AD) is the most common neurodegenerative disorder, causing 2/3 of dementia. 11% of the population over 65 years old suffer from the AD, and AD is the 4th leading cause to death in the aging population. However, the cause and mechanisms leading to AD remain elusive. The world is facing a dementia epidemic without effective prevention and treatment. Intensive researches have suggested the brain accumulation of the amyloid-beta protein (Abeta) as the initial event and deposition of Abeta to form neuritic plaques in the brain is the pathological hallmark of AD process. Over the past 15 years, several drugs that targeting Abeta have been tested in AD patients but with no satisfactory results. These disappointing efforts encourage us to think from a broader perspective, perhaps from the "seeds" during development. We focus on the role of a new gene CNTNAP2 in AD development. CNTNAP2 has been shown to play important roles in brain development. Abnormal CNTNAP2 expression and its genetic variations have been found in the brains of AD patients. These evidences encourage us to investigate how abnormal CNTNAP2 during development contributes to AD pathogenesis in the aging stage. Previously we demonstrated that hypoxia, primarily caused by vascular events in aging population, facilitates AD pathogenesis. Our study showed that CNTNAP2 gene expression is tightly regulated by hypoxia condition. Our study indicates that CNTNAP2 may serve as a new key molecule mediating stroke-induced dementia. The study provides novel insights into AD pathogenesis.