In the brains of Alzheimer¡¯s disease patients, the levels of a small protein fragment, called amyloid ¥â-peptide (A¥â), are highly elevated. Researchers have found that A¥â directly interferes with the normal function of brain nerve cells, resulting in the impairment of memory, which is a common feature of Alzheimer¡¯s disease. Our studies reveal that increasing the level of a specific membrane lipid, called PIP2, by one of the lipid kinases, known as PI4KII¥á, protects the nerve cells against the harmful A¥â effects. Furthermore, an activator of PI4KII¥á not only protects neurons from A¥â, but also inhibits A¥â production by the nerve cells. Thus, small molecules that can enhance the activity of PI4KII¥á may reduce the A¥â levels and protect neurons at the same time. Accordingly, our proposed study will attempt to identify small molecule activators of PI4KII¥á as potential therapeutic candidates for the treatment of Alzheimer¡¯s disease, that could potentially provide both symptomatic and disease-modifying therapeutic benefits.