Patterns of aberrant sprouting in Alzheimer's disease.
Alzheimer's disease (AD) is characterized by extensive synaptic and neuronal loss and by plaque formation in the cortex, but the mechanisms responsible for synaptic plasticity in the neocortex are still not completely understood. To analyze the sprouting response in AD cortex, we compared the patterns of GAP-43 with synaptophysin immunoreactivity. In AD, GAP-43 immunohistochemistry revealed extensive sprouting in the hippocampal molecular layer, stratum polymorphous, CA1 region, and prosubiculum. These regions presented abundant anti-GAP-43-immunoreactive coiled fibers and dystrophic neurites in association with plaques. Some of these sprouting structures were colocalized with anti-synapto-physin- and anti-neurofilament-positive neurites. The AD neocortex was characterized by an overall decrease in GAP-43 immunoreactivity accompanied by sprouting neurites in the areas of synaptic pathology. We conclude that GAP-43 might be involved in the mechanisms of synaptic plasticity in the AD cortex, as well as in the process of aberrant sprouting in the neuritic plaques.
Masliah
E
E
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093-0624.
Mallory
M
M
Hansen
L
L
Alford
M
M
Albright
T
T
DeTeresa
R
R
Terry
R
R
Baudier
J
J
Saitoh
T
T
D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D019922:GAP-43 Protein; D006133:Growth Substances / Q000276:immunology / Q000378:metabolism; D006624:Hippocampus / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D009454:Neurofibrils / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D016708:Synaptophysin
D019922:GAP-43 Protein; D006133:Growth Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016708:Synaptophysin