Additive Toxicity of b-Amyloid by a Novel Bioactive Peptide In Vitro: Possible Implications for Alzheimer’s Disease

Background: b-amyloid is regarded as a significant factor in Alzheimer’s disease: but inefficient therapies based on this rationale suggests that additional signalling molecules or intermediary mechanisms must be involved in the actual initiation of the characteristic degeneration of neurons. One clue could be that acetylcholinesterase, also present in amyloid plaques, is aberrant in peripheral tissues such as blood and adrenal medulla that can be implicated in Alzheimer’s disease. The aim of this study was to assess the bioactivity of a fragment of acetylcholinesterase responsible for its non-enzymatic functions, a thirty amino acid peptide (‘‘T30’’) which has homologies with b-amyloid. Methods: Cell viability was measured by sulforhodamine B assay and also lactate dehydrogenase assay: meanwhile, changes in the status of living cells was monitored by measuring release of acetylcholinesterase in cell perfusates using the Ellman reagent. Findings: T30 peptide and b-amyloid each have toxic effects on PC12 cells, comparable to hydrogen peroxide. However only the two peptides selectively then evoke a subsequent, enhanced release in acetylcholinesterase that could only be derived from the extant cells. Moreover, unlike hydrogen peroxide, the T30 peptide selectively shifted a sub-threshold dose of b-amyloid to a toxic effect, which also resulted in a comparable enhanced release of acetylcholinesterase. Interpretation: This is the first study comparing directly the bioactivity of b-amyloid with a peptide derived fro