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(American Journal of Pathology. 2004;164:2163-2174.)
© 2004 American Society for Investigative Pathology

Acetylcholinesterase-Aß Complexes Are More Toxic than Aß Fibrils in Rat Hippocampus

Effect on Rat ß-Amyloid Aggregation, Laminin Expression, Reactive Astrocytosis, and Neuronal Cell Loss

From the Centro de Regulación Celular y Patología "Joaquín V. Luco," Millennium Institute of Fundamental and Applied Biology, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

Neuropathological changes generated by human amyloid-ß peptide (Aß) fibrils and Aß-acetylcholinesterase (Aß-AChE) complexes were compared in rat hippocampus in vivo. Results showed that Aß-AChE complexes trigger a more dramatic response in situ than Aß 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 Aß aggregation in vitro as shown by turbidity measurements, Congo Red binding, as well as electron microscopy, suggesting that Aß-AChE deposits observed in vivo probably recruited endogenous Aß peptide; 2) the appearance of laminin expressing neurons surrounding Aß-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 Aß-injected animals. We conclude that the hippocampal injection of Aß-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 Aß-AChE complexes are more toxic than Aß fibrils and that AChE triggered some of the neurodegenerative changes observed in Alzheimer’s disease brains.

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