Free Radical Scavengers Block the Actions of β-Amyloid on Neurons in Tissue Culture

Abstract

The invariable co-localization of s-amyloid, an insoluble polypeptide comprised of about 40 amino acids, with the neuritic plaques and neurofibrillary tangles that are characteristic of Alzheimer’s disease (AD), has focused considerable world-wide research activity on the role of s-amyloid in the progressive loss of synapses and neurons that is also characteristic of AD. s-Amyloid is toxic to neurons in tissue culture but generally only after aging for several days in solution when the initially soluble s-amyloid strands aggregate and form clumps. A fragment of s-amyloid, the amino acids in positions 25 to 35 of the 40 amino acids making up the s-amyloid found in the brains of Alzheimer’s patients, aggregates very rapidly in aqueous solution (Pike et al., 1993), and is cytotoxic to neurons in tissue culture (Kumar et al., 1994) without the aging process needed to develop the toxicity of s-amyloid. s-Amyloid 1 to 40 disrupts the regulation of intracellular calcium (Mattson et al., 1992) and it has been considered that this disruption of cytosolic calcium is responsible for the neurotoxic actions of s-amyloid.