This PA, Drug Discovery for the Treatment of Alzheimer's Disease, is related to the priority area of chronic disabling conditions. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this PA may not exceed five years. Although this program is provided for in the financial plans of the NIA and the NIMH, the award of grants pursuant to this PA is also contingent upon the availability of funds for this purpose. The disease presents enormous problems not only to affected individuals but also to their families and raises many complex social and economic issues for the country.
AD provides a complex neurobiological puzzle.
Its etiology is not known, and the pathobiological processes that underlie the steady progression of the clinical course of this disease are not yet completely understood. It is clear, however, that mechanisms of cell to cell communication are disrupted. These involve several different types of neurotransmitter, neuropeptide, and neuromodulator systems, neurochemical processes, protein trafficking, and elements of oxidative and cellular energy metabolism processes. The hallmark of the disease involves progressive cell dysfunction, cell loss, and the accumulation of a variety of abnormal protein and cytoskeletal abnormalities. At present it is still not known when and how the degenerative process begins, although a role in this process involving the amyloid precursor protein and amyloid beta protein as well as neurofibrillary pathology associated with the protein tau seems reasonable.