Implications of amyloid precursor protein and subsequent beta-amyloid production to the pharmacotherapy of Alzheimer's disease.

Alzheimer's disease is the most common type of dementia in older people. It is highly prevalent, affecting 35-45% of those aged 85 years or older. This disease has devastating consequences to patients, their families, caregivers, and the health care system. Much has been learned about its pathobiology, which has led to the beta-amyloid (Abeta) hypothesis. This hypothesis continues to be the predominant postulate of the pathobiology of Alzheimer's disease. Under this hypothesis, abnormal accumulation of Abeta is followed by a cascade of neurotoxic effects, which eventually result in neurodegeneration and development of Alzheimer's disease. This is thought to be the result of altered processing of the amyloid precursor protein (APP), preferentially by beta- and gamma-secretase enzymes rather than nonamyloidogenic processing by alpha-secretase. The growing body of knowledge regarding the processing of APP to various forms of Abeta has resulted in new approaches to the investigation of putative anti-Alzheimer's disease compounds, including immune-based therapies and various agents that can positively affect APP processing.