Does the electrical activity of neurons contribute to the pathogenesis of Alzheimer’s Disease?

Abstract

Alzheimer's Disease is believed to be caused by the formation of amyloid fibrils formed by peptides of around 40 amino acid residues resulting from enzymatic cleavage of amyloid precursor protein (APP). The major components of those fibrils have been found to have a mainly alpha-helix conformation in apolar solutions and a looser structure in aqueous environments, while the amyloid fibrils are mostly beta-sheet. Major changes in secondary structure have been observed in other systems and are caused by various factors, including temperature, pH, and electric fields. The APP fragments, which form the amyloid fibrils, are known to migrate into the interneuronal synapses where they would be subjected to electric fields due to neuronal activity. We propose that the electrical activity of neurons causes a structural destabilization of the fragments, which could lead to fibril formation, and thereby contributes to the pathogenesis of Alzheimer's Disease.