Phospholipases as mediators of amyloid beta peptide neurotoxicity: An early event contributing to neurodegeneration characteristic of Alzheimer's disease

There is a consensus that by some still to be defined mechanism amyloid beta peptide, which accumulates in Alzheimer's disease brain tissue, contributes to the characteristic neurodegeneration. We suggest that one of these mechanisms for amyloid beta peptide is the ability to activate cellular phospholipases. Excessive phospholipid hydrolysis would produce a variety of lipidic second messengers. These catabolites would then evoke unnecessary stereotypic responses. This indiscriminate activation of the phospholipases could be responsible for the increased amounts of phospholipid catabolites found in Alzheimer's disease brain tissue. Failure to maintain regeneration of the membrane components would result in a loss of essential cellular neuronal processes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.