A NOVEL PEPTIDE PIVOTAL IN ALZHEIMER’S DISEASE: IN VIVO EVIDENCE IN A RAT MODEL

Abstract

Previous observations in vitro have suggested that a peptide derived from the C-terminus of acetylcholinesterase (AChE) could be a pivotal molecule in an excitotoxic mechanism underlying the neurodegenerative diseases (Greenfield, 2013). We now report here in vivobioactivity of this key peptide, inducing behavioural and histological effects in the rat following unilateral, intracerebral administration of the AChE peptide at concentrations of 100 nM, 1 μM or 100 μM into the basal forebrain, the initial site of cell loss in Alzheimer's disease (Schmitz et al., 2016). Six days after chronic treatment with the AChE peptide (1 injection/week for 3 weeks), behavioural changes were detected by using the Cylinder Test Performance where animals were observed for 5 minutes. Following the behavioural testing, permeability of the blood brain barrier was compared between the different groups using FITC-labeled albumin and visualised the FITC-albumin leakage on a fluorescent microscope. Treatment with T30 induces contralateral forelimb motor deficit, suggestive of general neurological impairment and not seen with vehicle alone: consistent with this pathological scenario, administration of the higher doses of peptide (1 μM or 100 μM) also enhanced the permeability of the blood-brain barrier as seen from an increase in fluorescent albumin signal in sections of basal forebrain. In summary, it appears that chronic T30 treatment has a selective toxicity in vivo that may throw light on a novel signalling system relevant to the neurodegenerative process.