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

Joseph D. Buxbaum, Gopal Thinakaran, Vassilis Koliatsos, James O'Callahan, Hilda H. Slunt, Donald L. Price, Sangram S. Sisodia

Research output: Contribution to journalArticlepeer-review

Abstract

Amyloid deposition is a neuropathological hallmark of Alzheimer's disease. The principal component of amyloid deposits is β amyloid peptide (Aβ), 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 Aβ 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 Aβ 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 Aβ domain accumulate, suggesting that these species may represent the penultimate precursors of synaptic Aβ.

Original languageEnglish (US)
Pages (from-to)9629-9637
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number23
DOIs
StatePublished - Dec 1 1998

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Axonal transport
  • Entorhinal cortex
  • Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)

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