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PMID: 9822724 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 18 ·No. 23 ·1998-12-01 ·Pages 9629-37

Buxbaum JD, Thinakaran G, Koliatsos V, O'Callahan J, Slunt HH, Price DL, Sisodia SS

Abstract

Amyloid deposition is a neuropathological hallmark of Alzheimer's disease. The principal component of amyloid deposits is beta amyloid peptide (Abeta), a peptide derived by proteolytic processing of the amyloid precursor protein (APP). APP is axonally transported by the fast anterograde component. Several studies have indicated that Abeta deposits occur in proximity to neuritic and synaptic profiles. Taken together, these latter observations have suggested that APP, axonally transported to nerve terminals, may be processed to Abeta at those sites. To examine the fate of APP in the CNS, we injected [35S]methionine into the rat entorhinal cortex and examined the trafficking and processing of de novo synthesized APP in the perforant pathway and at presynaptic sites in the hippocampal formation. We report that both full-length and processed APP accumulate at presynaptic terminals of entorhinal neurons. Finally, we demonstrate that at these synaptic sites, C-terminal fragments of APP containing the entire Abeta domain accumulate, suggesting that these species may represent the penultimate precursors of synaptic Abeta.

MeSH Terms
Amyloid beta-Peptides/analysis,genetics,metabolism Animals Axonal Transport/physiology Blotting, Western COS Cells Dentate Gyrus/chemistry,metabolism Methionine/pharmacology Neurons/chemistry,metabolism Perforant Pathway/chemistry,metabolism Presynaptic Terminals/chemistry,metabolism RNA, Messenger/analysis Rats Sulfur Radioisotopes
Chemicals
Amyloid beta-Peptides RNA, Messenger Sulfur Radioisotopes Methionine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Buxbaum J D
Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Thinakaran G
Koliatsos V
O'Callahan J
Slunt H H
Price D L
Sisodia S S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1998-12-01
Pages
9629-37
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6793291
Subset
IM
Grants
NIA NIH HHS · P50 AG005146 · United States
NIA NIH HHS · AG14996 · United States
NIA NIH HHS · AG 05146 · United States
NINDS NIH HHS · NS 20471 · United States
External Links
PubMed source PMC Full Text View journal details
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