2011 Grants - Di Paolo

Role of Phospholipase D1 in Alzheimer's Disease Pathogenesis

Gilbert Di Paolo, Ph.D.
Columbia University Medical Center
New York, New York

2011 Investigator-Initiated Research Grant

A characteristic feature of Alzheimer's pathology is the accumulation of beta-amyloid, a protein fragment that forms amyloid plaques in the brains of Alzheimer's patients. Beta-amyloid is formed from its parent protein, amyloid precursor protein (APP). In recent years, scientists have found evidence that the location of APP within cells affects the formation of beta-amyloid.

Phospholipase D1 (PLD1) is an enzyme inside many cells that influences the transport of APP to specific parts of a cell. Gilbert Di Paolo, Ph.D. and colleagues have preliminary evidence that PLD1 can be found in some of the same parts of cells in which APP is found, and where APP is processed to form beta-amyloid.

Dr. Di Paolo and colleagues have proposed to study how PLD1 affects the transport and processing of APP in nerve cells of the brain. Using mice that have been genetically altered so that PLD1 is missing, the researchers plan to characterize how loss of PLD1 affects the localization of APP and its processing into beta-amyloid. The researchers will also examine other genetic mouse models of Alzheimer's disease to determine how loss of PLD1 affects brain function. These studies will improve our understanding of a molecular pathway implicated in the development of Alzheimer's pathology, and they may help in the identification of targets for drugs to combat this process.