Monoclonal antibody Tor 23 binds a subset of neural cells in the human cortex and displays an altered binding distribution in Alzheimer's disease.
Recent evidence suggests that alterations in molecules of the external neuronal surface may be pivotal factors in Alzheimer's disease (AD) either as primary or secondary lesions. We are studying neuronal surface components with a library of monoclonal antibodies (MAbs) made to highly purified, exclusively cholinergic nerve terminals of the Torpedo ray. The most extensively characterized of the Tor MAbs. Tor 23, binds the external membrane of some human neuronal cells in culture. Our present findings demonstrate that Tor 23, in situ, binds the apparent limiting membrane of rare neurons of the human isocortex. Tor 23 binds, in addition, internally within a subpopulation of subcortical white matter astrocytes, as identified by colocalization with glial fibrillary acidic protein. Neuronal surface binding of Tor 23 parallels our findings in other species: astrocyte staining was not observed in other species and may be unique to human. Immunoblot analysis of white matter reveals one polypeptide band with a relative mobility of 115,000 +/- 15,000 daltons. In the mid-frontal cortex from cases of AD. Tor 23 immunopositive neurons are greatly reduced in number and immunopositive astrocytes are completely absent. The reduction of the neuronal surface epitope defined by Tor 23 supports the recent hypothesis that surface molecules are altered in AD. The absence of Tor 23 positive astrocytes opens an area for specific investigation: namely, the role subcortical astrocytes may play in the pathogenesis of AD.
Kushner
P D
PD
ALS Research Center, Pacific Presbyterian Medical Foundation, Pacific Presbyterian Medical Center, San Francisco, California 94115.
Stephenson
D T
DT
Wright
S
S
Cole
G M
GM
Greco
C M
CM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D002462:Cell Membrane / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D002794:Choline / Q000502:physiology; D004557:Electric Organ / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009411:Nerve Endings / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000473:pathology*; D014101:Torpedo / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D009419:Nerve Tissue Proteins; D002794:Choline