β-Amyloid protein-induced Alzheimer's disease animal model

doi:10.1016/0304-3940(94)90239-9

Neuroscience Letters

Volume 170, Issue 1, 28 March 1994, Pages 63-66

https://doi.org/10.1016/0304-3940(94)90239-9 Get rights and content

Abstract

To investigate the toxicity of β-amyloid protein which consisted of senile plaques of Alzheimer's disease (AD), this was infused into cerebral ventricle for 14 days by using mini-osmotic pump. The performance of the water maze task in β-amyloid protein-treated rats was impaired. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus. These results suggest that the deposition of β-amyloid protein in the brain is related to the impairment of learning and cholinergic neuronal degeneration, and that β-amyloid protein-treated rats could be used as an animal model for AD.

References (22)

C.R. Abraham et al.
Immunochemical identification of the serine protease inhibitor α_1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease
Cell
(1988)
J.J. Freeman et al.
Microsomal metabolism of acetonitrile to cyanide
Biochem. Pharmacol.
(1988)
N. Kaneda et al.
Highly sensitive assay for choline acetyltransferase activity by high-performance liquid chromatography with electrochemical detection
J. Chromatogr.
(1985)
J.Y. Koh et al.
β-Amyloid protein increases the vulnerability of cultured cortical neurons to cytotoxic damage
Brain Res.
(1990)
D.M. Mann et al.
Correlation between senile plaque and neurofibrillary tangle counts in cerebral cortex and neuronal counts in cortex and subcortical structures in Alzheimer's disease
Neurosci. Lett.
(1985)
R. Morris
Development of a water-maze procedure for studing spatial learning in the rat
J. Neurosci. Methods
(1984)
T. Nabeshima et al.
Memory impairment and morphological changes in rats induced by active fragment of anti-nerve growth factor-antibody
Biochem. Biophys. Res. Commun.
(1991)
A. Nitta et al.
Effects of oral administration of a stimulator for nerve growth factor synthesis in basal forebrain-lesioned rats
Eur. J. Pharmacol.
(1993)
C.J. Pike et al.
In vitro aging of β-amyloid protein causes peptide aggregation and neurotoxicity
Brain Res.
(1991)
J. Waite et al.
Solvent effects on beta protein toxicity in vivo
Neurobiol. Aging
(1992)

G.K. Wilcock et al.

Plaques, tangles and dementia

A quantitative study

J. Neurol. Sci.

(1982)

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β-Amyloid protein-induced Alzheimer's disease animal model

Abstract

Cell

Biochem. Pharmacol.

J. Chromatogr.

Brain Res.

Neurosci. Lett.

J. Neurosci. Methods

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

Brain Res.

Neurobiol. Aging

J. Neurol. Sci.