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 bet a peptide, which accumulates in Alzheimer's disease brain tissue, contribut es to the characteristic neurodegeneration. We suggest that one of these me chanisms for amyloid beta peptide is the ability to activate cellular phosp holipases. Excessive phospholipid hydrolysis would produce a variety of lip idic second messengers. These catabolites would then evoke unnecessary ster eotypic responses. This indiscriminate activation of the phospholipases cou ld be responsible for the increased amounts of phospholipid catabolites fou nd in Alzheimer's disease brain tissue. Failure to maintain regeneration of the membrane components would result in a loss of essential cellular neuro nal processes. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.