Acetylcholinesterase-Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss.
Neuropathological changes generated by human amyloid-beta peptide (Abeta) fibrils and Abeta-acetylcholinesterase (Abeta-AChE) complexes were compared in rat hippocampus in vivo. Results showed that Abeta-AChE complexes trigger a more dramatic response in situ than Abeta 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 Abeta aggregation in vitro as shown by turbidity measurements, Congo Red binding, as well as electron microscopy, suggesting that Abeta-AChE deposits observed in vivo probably recruited endogenous Abeta peptide; 2). the appearance of laminin expressing neurons surrounding Abeta-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 Abeta-injected animals. We conclude that the hippocampal injection of Abeta-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 Abeta-AChE complexes are more toxic than Abeta fibrils and that AChE triggered some of the neurodegenerative changes observed in Alzheimer's disease brains.
Reyes
Ariel E
AE
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.
Chacón
Marcelo A
MA
Dinamarca
Margarita C
MC
Cerpa
Waldo
W
Morgan
Carlos
C
Inestrosa
Nibaldo C
NC
D000110:Acetylcholinesterase / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007797:Laminin / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D000110:Acetylcholinesterase