Acetylcholinesterase-Aβ complexes are more toxic than Aβ fibrils in rat hippocampus: Effect on rat β-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss

Ariel E. Reyes, Marcelo A. Chacón, Margarita C. Dinamarca, Waldo Cerpa, Carlos Morgan, Nibaldo C. Inestrosa

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Neuropathological changes generated by human amyloid-β peptide (Aβ) fibrils and Aβ-acetylcholinesterase (Aβ-AChE) complexes were compared in rat hippocampus in vivo. Results showed that Aβ-AChE complexes trigger a more dramatic response in situ than Aβ fibrils alone as characterized by the following features observed 8 weeks after treatment: 1) amyloid deposits were larger than those produced in the absence of AChE. In fact, AChE strongly stimulates rat Aβ aggregation in vitro as shown by turbidity measurements, Congo Red binding, as well as electron microscopy, suggesting that Aβ-AChE deposits observed in vivo probably recruited endogenous Aβ peptide; 2) the appearance of laminin expressing neurons surrounding Aβ-AChE deposits (such deposits are resistant to disaggregation by laminin in vitro); 3) an extensive astrocytosis revealed by both glial fibrillary acidic protein immunoreactivity and number counting of reactive hypertrophic astrocytes; and 4) a stronger neuronal cell loss in comparison with Aβ-injected animals. We conclude that the hippocampal injection of Aβ-AChE complexes results in the appearance of some features reminiscent of Alzheimer-like lesions in rat brain. Our studies are consistent with the notion that Aβ-AChE complexes are more toxic than Aβ fibrils and that AChE triggered some of the neurodegenerative changes observed in Alzheimer's disease brains.

Original languageEnglish
Pages (from-to)2163-2174
Number of pages12
JournalAmerican Journal of Pathology
Volume164
Issue number6
DOIs
Publication statusPublished - 1 Jan 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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