Acetylcholinesterase Enhances the Neurotoxicity of β-Amyloid Fibrils

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder which hallmark is the presence of senile plaques and neurofibrillary tangles. The senile plaques are mainly composed of β-amyloid (Aβ) fibrils and some proteins including acetylcholinesterase (AChE) are also localized with these deposits. AChE has demonstrated a strong capability to increase the aggregation of Aβ-peptide (Aβ_1–40) (1) and to be cytotoxic (2). In the present work we have studied the neurotoxicity in vitro of β-amyloid fibrils containing AChE. Aβ_1–40 and Aβ, _1–42 peptides were incubated in absence/presence of AChE (G₄ from bovine nucleus caudatus). The fibrils were characterized by turbidometry and specific stains, and added to preseeded PC12 cells. Neurotoxicity was measured by the MTT-reduction method. Results indicate that fibrils containing AChE are more toxic than those without the enzyme for both peptides. Subsequently, Aβ_1–40 peptide was induced to aggregate with increasing concentrations of AChE. When the neurotoxicity of these fibrils was evaluated, we found that the neurotoxicity enhancement depends on the amount of AChE contained in the fibrils. Our results suggest that AChE should play an important role in the neurode-generation induced by Aβ deposits in AD.