Marta Lipinski, Ph.D.
Harvard Medical School
Cambridge, Massachusetts

2003 New Investigator Research Grant

Many scientists believe that the signature pathological event in Alzheimer’s disease is abnormal processing of amyloid precursor protein (APP) to produce the protein fragment beta-amyloid. An emerging body of research suggests that a family of enzymes called caspases may make a key contribution to this abnormal processing pathway. Caspases are also critical to programmed cell death (apoptosis), an orderly biochemical sequence that eliminates diseased cells from the body. Disruptions in programmed cell death are thought to play an important role in cancer, Alzheimer’s, and other diseases. Involvement of caspases in both abnormal APP processing and programmed cell death suggests that drugs that block these enzymes might hold promise as a new class of Alzheimer treatments.

Exploration of the value of caspases as potential drug targets will require substantial additional information about their identity and function. These researchers will design genetically engineered mice to serve as a living system in which to investigate which caspases are involved in APP processing and to assess the impact of various caspases involved in programmed cell death. Insights gained may lay important groundwork for developing a new class of Alzheimer drugs.