Vulnerability of small GABAergic neurons to human β-amyloid pentapeptide

• Published in: Brain research 1998-06, Vol.796 (1), p.239-246
• Main Authors: Pakaski, Magdolna, Farkas, Zoltan, Kasa, Peter, Forgon, Monika, Papp, Henrietta, Zarandi, Marta, Penke, Botond
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid; Amyloid beta-Peptides - pharmacology; Amyloid beta-Peptides - poisoning; Animals; Apoptosis - physiology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Drug Resistance; GABA immunocytochemistry; gamma-Aminobutyric Acid - physiology; Humans; Image analysis; Image Processing, Computer-Assisted; Immunohistochemistry; Medical sciences; Microscopy, Electron, Scanning; Neurology; Neuronal culture; Neurons - diagnostic imaging; Neurons - drug effects; Neurons - physiology; Peptide Fragments - pharmacology; Peptide Fragments - poisoning; Rats - embryology; Scanning electron microscopy; Ultrasonography
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(98)00358-8

β-Amyloid peptide (A β), the principal component of senile plaques in Alzheimer's disease, has been found to be neurotoxic. The role of A β in the deficits of the GABAergic system in patients with Alzheimer's disease is unclear. It has been suggested that the cytotoxic activity of A β is localized to amino acid residues 25–35 of this peptide, which contains a total of 42 amino acid residues. We now report that the short amyloid peptide fragments corresponding to amino acids 31–35 (A β31–35) and 34–39 (A β34–39) are also toxic in vitro to the small GABAergic neuron population of basal forebrain cultures. Morphological changes were accompanied by an increased number of varicosities localized on the processes of the GABA-immunoreactive neurons and by the appearance of round cells without processes. The neurodegeneration was confirmed by means of scanning electron microscopy. Quantification of the morphological findings by image analysis demonstrated a size-related dependence of the degeneration of GABAergic neurons. The results suggest that fragments of A β shorter than A β25–35 may exert cytotoxic action and demonstrate the toxicity of these A β fragments in decreasing the number of small GABAergic neurons.