In vivo neurotoxicity of beta-amyloid [beta(1-40)] and the beta(25-35) fragment.
We examined the histological changes produced by injections of beta-amyloid [beta(1-40)], and control peptides in rat and monkey cerebral cortex. beta(25-35) injections were also studied in rat cortex. Standard immunoperoxidase procedures were used to detect the distribution of tau, MAP2, beta(1-40) and ALZ 50 immunoreactivity. All injections produced localized necrosis at the injection site surrounded by a zone of neuronal loss and gliosis. In rat cortex, lesions produced by solubilized beta(1-40) and beta(25-35) in water were generally larger than those produced by control peptides. Tau and ALZ 50 antibodies labeled neurites and diffusely positive perikarya around beta(1-40) injections, whereas MAP2 staining was reduced, paralleling the distribution of neuronal loss and gliosis. In aged primate cortex, beta(1-40) lesion size was dose dependent. Hyalinized, ALZ 50 positive neurons, and abnormal neurites were prominent around the injection site. Although beta-amyloid is acutely neurotoxic in both rat and monkey cerebral cortex, neuronal degeneration in the primate more closely resembles that found in AD.
Kowall
N W
NW
Neurology Service, Massachusetts General Hospital, Boston 02115.
McKee
A C
AC
Yankner
B A
BA
Beal
M F
MF
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D048588:Benzoxazines; D002540:Cerebral Cortex / Q000473:pathology; D003599:Cytoskeleton / Q000737:chemistry; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D009336:Necrosis; D009410:Nerve Degeneration / Q000187:drug effects; D010078:Oxazines; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D048588:Benzoxazines; D010078:Oxazines; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C028911:cresyl violet