VULNERABILITY OF SMALL GABAERGIC NEURONS TO HUMAN BETA-AMYLOID PENTAPEPTIDE

beta-Amyloid peptide (A beta), the principal component of senile plaqu es in Alzheimer's disease, has been found to be neurotoxic. The role o f Ap in the deficits of the GABAergic system in patients with Alzheime r's disease is unclear. It has been suggested that the cytotoxic activ ity of A beta is localized to amino acid residues 25-35 of this peptid e, which contains a total of 42 amino acid residues. We now report tha t the short amyloid peptide fragments corresponding to amino acids 31- 35 (A beta 31-35) and 34-39 (A beta 34-39) are also toxic in vitro to the small GABAergic neuron population of basal forebrain cultures. Mor phological changes were accompanied by an increased number of varicosi ties localized on the processes of the GABA-immunoreactive neurons and by the appearance of round cells without processes, The neurodegenera tion was confirmed by means of scanning electron microscopy. Quantific ation of the morphological findings by image analysis demonstrated a s ize-related dependence of the degeneration of GABAergic neurons. The r esults suggest that fragments of A beta shorter than A beta 25-35 may exert cytotoxic action and demonstrate the toxicity of these A beta fr agments in decreasing the number of small GABAergic neurons. (C) 1998 Elsevier Science B.V. All rights reserved.