 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 15, 4896-4905, Copyright © 1995 by Society for Neuroscience
Chronic elevation of secreted amyloid precursor protein in subcortically lesioned rats, and its exacerbation in aged rats
WC Wallace, I Lieberburg, D Schenk, C Vigo-Pelfrey, KL Davis and V Haroutunian
Laboratory of Biochemical Genetics, NIMH, Washington, DC, USA.
Subcortically lesioned rats were used as an animal model of some of the
neurochemical and behavioral deficits of Alzheimer's disease (AD) to
investigate the in vivo expression and metabolism of amyloid precursor
protein (APP). Previously, the rapid and persistent induction of APP was
described in cerebral cortices after disruption of its cholinergic,
serotonergic, or noradrenergic afferents. In the present study, this
induction was found to lead to the elevated secretion of APP into the
cerebrospinal fluid of lesioned animals. Lesions of the forebrain
cholinergic system in aged rats caused an even greater increase in the CSF
levels of secreted APP. Antibodies to the extracellular domain of APP
detected the protein whereas antibodies to the cytoplasmic region did not,
indicating that the APP present in CSF was of the soluble form.
Immunoprecipitation with an A beta sequence-specific antibody followed by
immunoblot analysis indicated that a significant portion of secreted APP
was of the species that contains at least the first 28 amino acids of the A
beta sequence (APP gamma or APPA beta). By contrast, very low levels of A
beta peptide were detected in CSF. The secretion was accompanied by an
elevation of cellular C-terminal fragments of the APP in the lesioned
cortex. Consistent with our previous results, this increased APP secretion
was caused by lesions of subcortical cholinergic and serotonergic systems.
The postlesion time course of APP secretion showed an initial reduction of
APP (1 hr postlesion) in CSF followed by an eventual twofold elevation 1-6
weeks later. These results indicate that the induction of APP in response
to loss of subcortical innervation leads to elevated secretion of a soluble
form of cortically derived APP that contains significant portions of the A
beta sequence.
This article has been cited by other articles:
|
|
|
|
 
D. K. Lahiri, D. Chen, B. Maloney, H. W. Holloway, Q.-s. Yu, T. Utsuki, T. Giordano, K. Sambamurti, and N. H. Greig
The Experimental Alzheimer's Disease Drug Posiphen [(+)-Phenserine] Lowers Amyloid-beta Peptide Levels in Cell Culture and Mice
J. Pharmacol. Exp. Ther.,
January 1, 2007;
320(1):
386 - 396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Utsuki, Q.-s. Yu, D. Davidson, D. Chen, H. W. Holloway, A. Brossi, K. Sambamurti, D. K. Lahiri, N. H. Greig, and T. Giordano
Identification of Novel Small Molecule Inhibitors of Amyloid Precursor Protein Synthesis as a Route to Lower Alzheimer's Disease Amyloid-beta Peptide
J. Pharmacol. Exp. Ther.,
August 1, 2006;
318(2):
855 - 862.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. K. LAHIRI, T. UTSUKI, D. CHEN, M. R. FARLOW, M. SHOAIB, D. K. INGRAM, and N. H. GREIG
Nicotine Reduces the Secretion of Alzheimer's {beta}-Amyloid Precursor Protein Containing {beta}-Amyloid Peptide in the Rat without Altering Synaptic Proteins
Ann. N.Y. Acad. Sci.,
June 1, 2002;
965(1):
364 - 372.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Felician and T. A. Sandson
The Neurobiology and Pharmacotherapy of Alzheimer's Disease
J Neuropsychiatry Clin Neurosci,
February 1, 1999;
11(1):
19 - 31.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Zhao, L. Paganini, L. Mucke, M. Gordon, L. Refolo, M. Carman, S. Sinha, T. Oltersdorf, I. Lieberburg, and L. McConlogue
beta -Secretase Processing of the beta -Amyloid Precursor Protein in Transgenic Mice Is Efficient in Neurons but Inefficient in Astrocytes
J. Biol. Chem.,
December 6, 1996;
271(49):
31407 - 31411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
