Neurotoxicity and oxidative damage of beta amyloid 1-42 versus beta amyloid 1-40 in the mouse cerebral cortex.
Senile plaques (SP), a neuropathological hallmark of Alzheimer's disease (AD), are characterized by extracellular accumulations of beta amyloid (A beta). SP predominantly contain A beta 42 with a small amount of associated A beta 40. We determined the neurotoxic properties of A beta 42 as compared to A beta 40 by injections into the frontal cortex of three month old C57BL/6 mice. A beta 42 was associated with a significantly larger area of glial fibrillary acidic protein (GFAP) immunoreactivity and a greater density of reactive astrocytes than A beta 40. Immunohistochemical staining for markers of oxidative damage against 3-nitrotyrosine (3-NT) and 8-hydroxydeoxyguanosine (8-OHDG) were significantly more intense around the A beta 42 injection compared to the A beta 40 injection sites. These findings are consistent with previous in vitro studies and suggest that A beta 42 is more neurotoxic and may generate more free radical damage than A beta 40.
Klein
A M
AM
Department of Neurology, Boston University School of Medicine, Massaschusetts 02118, USA.
Kowall
N W
NW
Ferrante
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005609:Free Radicals / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D005904:Glial Fibrillary Acidic Protein; D009498:Neurotoxins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine