The 14-3-3 protein detectable in the cerebrospinal fluid of patients with prion-unrelated neurological diseases is expressed constitutively in neurons and glial cells in culture

The 14-3-3 protein belongs to a family of 30-kD proteins originally identif ied by two-dimensional analysis of brain protein extracts. Recently, the de tection of the 14-3-3 protein in the cerebrospinal fluid (CSF) is utilized as a highly reliable test for the premortem diagnosis of prion diseases suc h as Creutzfeldt-Jakob disease. For the initial step, to clarify the biolog ical implication of the CSF 14-3-3 protein in these diseases, its expressio n was investigated in neural tissues and cultures and CSF samples from pati ents with a variety of neurological diseases by Western blot analysis and i mmunocytochemistry, The constitutive expression of the 14-3-3 protein was i dentified in ail neural and nonneural tissues examined. It was expressed in all neurons,astrocytes, oligodendrocytes, and microglia in culture with it s location in both cytoplasmic and nuclear regions. The 14-3-3 protein was detected in the CSF of 8 out of 71 patients, including 1 Gerstmann-Straussl er-Scheinker disease patient and 7 patients with prion;unrelated neurologic al diseases, such as meningoencephalitis of viral, bacterial, or tuberculou s origin, multiple sclerosis, and mitochondrial myopathy, encephalopathy, l actic acidosis, and strokelike episodes. These results suggest that the 14- 3-3 protein expressed constitutively at substantial levels in both neurons and glial cells might be released into the CSF as a disease-nonspecific con sequence of the extensive brain damage and indicate that the analysis of th e 14-3-3 protein in the CSF is not useful as a screening test for prion dis eases.