A NOVEL PEPTIDE PIVOTAL IN ALZHEIMER’S DISEASE: A POTENTIAL BIOMARKER IN HUMAN BLOOD POSSIBLY LINKED TO COGNITIVE DECLINE?

Abstract

A C-terminal peptide derived from Acetylcholinesterase (AChE) is present as a naturally occurring bioactive molecule in brain tissue. We have previously shown that an antibody raised against this C-terminus peptide can selectively recognise this innate signalling molecule in brain tissue. The antibody displays significantly higher immunoreactivity in the developing rat brain compared with the more developed young adult rat brain whilst, the amount of AChE peptide immunoreactivity detectable is doubled in human brain in Alzheimer's disease compared to controls. The antibody, previously used to detect and quantify the AChE C-Terminus peptide in brain tissue by an indirect ELISA immunoassay, was employed to quantify relative levels of circulating endogenous peptide in human blood. Patients were grouped by their relative levels of AChE peptide (within the cohort) for the purposes of analysis. Immunoreactivity to this antibody appears to be modulated in relation to cognitive tests administered to cognitively healthy patients, patients with mild cognitive impairment (MCI), and suspected Alzheimer's patients. The selective immunoreactivity of the antibody to an endogenous AChE peptide present in both human plasma and serum suggests a potential biomarker of neurodegeneration is available in the human blood. Moreover, quantification of the peptide in this tissue may be a good predictor of disease and thus a potential diagnostic allowing for the possibility of earlier intervention.