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The Journal of Neuroscience, December 1, 1998, 18(23):9629-9637
Alzheimer Amyloid Protein Precursor in the Rat Hippocampus:
Transport and Processing through the Perforant Path
Joseph D.
Buxbaum1,
Gopal
Thinakaran2,
Vassilis
Koliatsos2, 4,
James
O'Callahan1, 5,
Hilda H.
Slunt2,
Donald L.
Price2, 3, 4, and
Sangram S.
Sisodia6
1 Laboratory of Molecular Neuropsychiatry, Department
of Psychiatry, Mount Sinai School of Medicine, New York, New
York 10029, Departments of 2 Pathology,
3 Neurology, and 4 Neuroscience, The Johns
Hopkins University School of Medicine, Baltimore, Maryland 21205, 5 Center for Disease Control and Prevention, National
Institute of Occupational Safety and Health, Morgantown, West Virginia
26505, and 6 Department of Pharmacological and
Physiological Sciences, The University of Chicago, Chicago, Illinois
60637
Amyloid deposition is a neuropathological hallmark of Alzheimer's
disease. The principal component of amyloid deposits is  amyloid peptide (A), 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 A 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 A 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 A domain
accumulate, suggesting that these species may represent the penultimate
precursors of synaptic A.
Key words:
Alzheimer's disease; axonal transport; A; amyloid
precursor protein; entorhinal cortex; hippocampus
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239629-09$05.00/0
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