Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGF beta 1 and TGF beta 2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGF beta 1 and total TGF beta 2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGF beta 1 and TGF beta 2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGF beta 1 (P = 0.015) and TGF beta 2 (P = 0.012) compared to normal controls. There was a trend for TGF beta 2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGF beta 1 or TGF beta 2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGF beta 1 may leak into the vCSF from plasma, Autopsy vCSF levels of TGF beta isoforms were found to be distinctly different from those reported for human serum, especially for TGF beta 2, which is undetectable in plasma. These results indicate that further in vivo studies of TGF beta 2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGF beta 2 concentrations. (C) 1996 Academic Press, Inc.