Altered processing of Alzheimer amyloid precursor protein in response to neuronal degeneration.
In the brains of individuals with Alzheimer disease, senile plaques containing aggregates of beta-amyloid peptide, derived from the beta-amyloid precursor protein (APP), are seen in association with degenerating nerve terminals. It is not known whether the degenerating nerve terminals cause the formation of these aggregates or whether beta-amyloid peptide in the aggregates causes nerve-terminal degeneration. In the present study of rat brain, degeneration either of local neurons or of nerve terminals caused decreased levels of a neuron-enriched isoform of APP, increased levels of a glia-enriched isoform of APP, and increased levels of potentially amyloidogenic, as well as nonamyloidogenic, COOH-terminal fragments of APP. Our results demonstrate that neuronal degeneration affects APP processing and suggest that it may contribute to amyloid formation in mammalian brain.
Iverfeldt
K
K
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Walaas
S I
SI
Greengard
P
P
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality; D007150:Immunohistochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017378:Quinolinic Acid