Vulnerability of small GABAergic neurons to human beta-amyloid pentapeptide.
beta-Amyloid peptide (A beta), the principal component of senile plaques in Alzheimer's disease, has been found to be neurotoxic. The role of A beta 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 beta 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 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. 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 beta shorter than A beta 25-35 may exert cytotoxic action and demonstrate the toxicity of these A beta fragments in decreasing the number of small GABAergic neurons.
Alzheimer's Disease Research Centre, Albert Szent-Györgyi Medical University, Szeged, Hungary. pakaski@comser.szote-u.szeged.hu
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D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000506:poisoning; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004351:Drug Resistance; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008855:Microscopy, Electron, Scanning; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000506:poisoning; D051381:Rats / Q000196:embryology; D014463:Ultrasonography; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C113042:amyloid beta-protein (31-35); C114962:amyloid beta-protein (34-39); D005680:gamma-Aminobutyric Acid