Oligoclonal bands and blood--cerebrospinal-fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis.

As known from inflammatory diseases, oligoclonal bands in the cerebrospinal fluid (CSF-OCB) may indicate a humoral immune response within the central nervous system. Previous studies on the CSF IgG content in Alzheimer disease (AD)have been controversial about the relationship of OCB and elevated IgG indices. To explore this problem, we combined qualitative (isoelectric focusing) and quantitative methods (IgG index) to detect intrathecal IgG production and related these findings to the presence of blood--cerebrospinal-fluid barrier (BCB) dysfunction. Fifty-one AD patients were compared with patients with vascular dementia (VD), major depression (MD), multiple sclerosis (MS), and age-matched control subjects. CSF-OCB could be traced in 20% of AD patients. An elevated IgG index was found in 6% and a BCB dysfunction in 16% of all AD patients. Either intrathecal IgG synthesis or BCB dysfunction were detected in a subgroup of 36% of all AD cases and in 40% of patients with late-onset AD. Intrathecal IgG synthesis and BCB dysfunction may suggest underlying immunological or inflammatory changes in an as-yet undefined subgroup of AD patients and support the notion of a heterogeneous nature of AD.

Detection of the novel cell adhesion molecule MUC18 in human brain tissue.

The implication of cell adhesion molecules (CAMs) in the mediation of the immune response to inflammatory stimuli has been shown in different neurological syndromes. The neural cell adhesion molecule (NCAM) and the myelin associated glycoprotein (MAG) are functionally important CNS-cell adhesion molecules (CAMs) and members of the immunoglobulin gene superfamily (IgSF). Both CAMs are expressed from the time of neuronal induction and myelin formation and are likely to contribute to the generally adhesive properties of neurons and oligodendrocytes. The present study describes, by means of SDS-PAGE and immunoblotting, a novel CNS antigen which is a glycoprotein detected in post mortem frontal lobe tissue of ten subjects at an M(r) 65 and 113 kD which showed the greatest sequence homology to neuronal IgSF members like NCAM. This expected membrane CAM, with probable functions in CNS cell-cell interactions, had been detected first in primary human melanoma cells, with increasing expression as tumors progress and is expected to be a developmentally regulated CAM in neuroectodermal tissues.

Fibrin degradation products in post mortem brain tissue of schizophrenics: a possible marker for underlying inflammatory processes.

Alterations in protein composition are often present in diseases of the central nervous system (CNS). Inflammatory processes causing these alterations have been suggested by many authors to underlie the cerebral disturbance in some cases of schizophrenia. In a previous study, two disease-associated additional polypeptides P1 and P2 could be detected in the cerebrospinal fluid (CSF) of 60 out of 123 (49%) schizophrenic patients. These polypeptides were identified as cleavage products of the beta-chain of fibrin(ogen), an acute-phase protein which is increased in inflammatory processes. Because investigations of brain tissue might better reflect the disease process than cerebrospinal fluid, we examined 6 post mortem brains (3 schizophrenics, 3 normal controls) for the presence of fibrin(ogen) and its cleavage products by two dimensional gel electrophoresis followed by immunoblotting. We detected fibrin(ogen) and its degradation products P1 and P2 in all schizophrenic brain tissue samples, but not in that from controls. These results are consistent with previous CSF observations and suggest that a CNS inflammatory process may be occurring in a subgroup of schizophrenic patients.