Physiological production of the beta-amyloid protein and the mechanism of Alzheimer's disease.

The progressive deposition of the beta-amyloid peptide in the brain and its microvasculature is an invariant feature of Alzheimer's disease that appears to precede the onset of dementia by many years. It had been assumed that the proteolytic release of beta-amyloid peptide from the transmembrane region of its large precursor protein was an aberrant event, requiring prior membrane injury. However, it has recently been shown that beta-amyloid peptide is continuously secreted from healthy neural and non-neural cells in culture and circulates in human CSF and blood. The finding that beta-amyloid peptide is a normal, soluble product of cellular metabolism has led to many dynamic studies of its formation and clearance in health and in genetic forms of Alzheimer's disease, and should facilitate the design of amyloid-inhibiting therapeutics.