ALZHEIMERS-DISEASE CEREBROSPINAL-FLUID ANTIBODIES DISPLAY SELECTIVITYFOR MICROGLIA - INVESTIGATIONS WITH CELL-CULTURES AND HUMAN CORTICAL BIOPSIES

Previous investigations demonstrated that the cerebrospinal fluid (CSF ) from Alzheimer's disease (AD) patients contains antibodies that reco gnize specific neuronal populations in the adult rat central nervous s ystem (CNS). These findings suggest a pathogenic role for immunologica l aberrations in this disorder. To determine if antibodies may provide a means to differentially diagnose the dementias, CSF from a diversif ied dementia population was screened against the developing rat CNS an d a cell culture system. Markings produced by AD CSF were distinctly d ifferent from those of vascular dementias (VAD) against the developing rat CNS. More importantly, some AD CSF recognized amoeboid microglia. The recognition of amoeboid microglia by antibodies in AD CSF is part icularly interesting since these cells proliferate in response to nerv ous system disease and also engulf debris. A cell culture technique wa s developed to allow the rapid screening of CSF antibodies. Patient CS F produced five different types of markings in the cell culture: micro glia, glioblasts, fibers, nonspecific, or negative. Correlations with these structures and the diagnosis of four different dementia populati ons revealed that, in comparison to the other groups, AD CSF displayed remarkable selectivity toward microglial cells. Cortical biopsies fro m patients suspected to have AD were incubated with the patient's own CSF and that of confirmed AD patients. Both CSF samples recognized mic roglial cells in the patient's cortical biopsy. The same CSF samples i ncubated against normal human cortical autopsy or a biopsy from a 3-mo -old child displayed negative immunoreactivity. These three approaches suggest that the presence of CSF microglial antibodies may be a means to distinguish AD patients from other dementias. The results add furt her support to the widely growing concept that inflammation and simila r immune mechanisms may contribute to AD pathogenesis.