An antibody against phosphorylated neurofilaments identifies a subset of damaged association axons in Alzheimer's disease.
We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to four-fold increase in neuronal SMI 312 immunolabeling, and neuropil neuritic processes were severely disrupted. Double-immunolabeling analysis showed that 88% of SMI 312-immunolabeled abnormal neuritic clusters were associated with amyloid, whereas the remaining 12% were not. Serial section analysis and 3-D reconstructions suggested that dystrophic neurites of classical plaques were derived from long axons. These abnormal neurites were also growth-associated protein 43 positive and occasionally tau positive. The present study supports the contention that a subpopulation of aberrantly sprouting axons in the neuritic plaque is derived from cortico-cortico fibers. This disruption of the neocortical association fibers and neuritic microcircuitry could underlie the cognitive impairment of Alzheimer's disease.
Masliah
E
E
University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla.
Mallory
M
M
Hansen
L
L
Alford
M
M
DeTeresa
R
R
Terry
R
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001369:Axons / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000276:immunology* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D010766:Phosphorylation
D000911:Antibodies, Monoclonal