Lack of Alzheimer pathology after beta-amyloid protein injections in rat brain.
In order to establish a direct relationship between beta-amyloid protein (beta AP) and in vivo neurotoxicity, we made intraparenchymal injections and Alzet pump infusions of beta AP into the hippocampus and cortex of adult rats. We tested a number of synthetic beta AP peptides (beta AP 1-40, 1-38, and 25-35) and peptide controls (scrambled and reversed 1-40, and scrambled and reversed 25-35) over a wide range of concentrations and in a variety of vehicles. The rats were sacrificed from 2-35 days following the implant, and the brains examined by standard immunohistochemical and histological methods used to evaluate the pathologies associated with Alzheimer's disease. We report the lack of Alzheimer related pathology and no significant morphological differences between the beta AP peptide and the peptide and vehicle control injections. These observations indicate that the simple intraparenchymal injection of beta AP in the rat brain is not an appropriate model of Alzheimer-related neurotoxicity.
Games
D
D
Athena Neurosciences, South San Francisco, CA 94080.
Khan
K M
KM
Soriano
F G
FG
Keim
P S
PS
Davis
D L
DL
Bryant
K
K
Lieberburg
I
I
D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex; D006624:Hippocampus; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D016612:Paraffin Embedding; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)