C-terminal fragments of amyloid-beta peptide cause cholinergic axonal degeneration by a toxic effect rather than by physical injury in the nondemented human brain.
Previous experimental studies have indicated that amyloid-beta peptide (Abeta) may cause axonal degeneration in the brain of individuals with Alzheimer's disease (AD) by physical injury, mass lesion, or membrane perturbation. In this study, acetylcholinesterase histochemical, and Abeta and tau immunohistochemical double-staining were performed in nondemented elderly human hippocampal and entorhinal brain samples, to demonstrate the presence of dystrophic neurites caused by the C-terminal or N-terminal fragments of Abeta. The early interactions between the Abeta-stained senile plaques (SPs) and the enzyme-positive axons were investigated. The double-stained samples revealed that Abeta deposition occurs first, followed by the development of cholinergic axonal damage. Most of the dystrophic axonal processes are incorporated in the peripheral area of the SPs and are positive for phosphorylated tau [pS202] and tau-5. The result suggests that C-terminal fragments are more harmful than N-terminal fragments of Abeta and may induce the development of dystrophic neurites by a toxic effect rather than by physical injury.
Kasa
Peter
P
Alzheimer's Disease Research Centre, Department of Psychiatry, University of Szeged, Hungary. kp@comser.szote.u-szeged.hu
Papp
Henrietta
H
Zombori
Janos
J
Mayer
Peter
P
Checler
Frederic
F
D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001369:Axons / Q000201:enzymology / Q000473:pathology*; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D002799:Cholinergic Fibers / Q000473:pathology*; D006801:Humans; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins; D000110:Acetylcholinesterase