THE 14-3-3-BRAIN-PROTEIN IN CEREBROSPINAL-FLUID AS A MARKER FOR TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

Background There is no practical and reliable premortem test for Creut zfeldt-Jakob disease and the related transmissible spongiform encephal opathies. Two proteins, designated 130 and 131, which have been detect ed in low concentrations in cerebrospinal fluid from patients with Cre utzfeldt-Jakob disease, appear to be sensitive and specific markers fo r the disease. Attempts to identify these proteins, however, have been unsuccessful. We hypothesized that they may be present in the normal brain. Methods We detected proteins 130 and 131 in normal human brain, partially sequenced their amino acids, and found that they matched th e brain protein known as 14-3-3. We then developed a simple, rapid imm unoassay for this protein and tested it in cerebrospinal fluid samples from 71 humans and 30 animals with spongiform encephalopathies and in control samples from 186 humans and 94 animals. Results The immunoass ay detected the 14-3-3 protein in cerebrospinal fluid from 68 of the 7 1 patients with Creutzfeldt-Jakob disease (96 percent; 95 percent conf idence interval, 92 to 99 percent). Among 94 patients with other demen tias, the specificity was 96 percent. If one excludes the three patien ts with dementia who had had strokes within one month before testing, the specificity was 99 percent. The test was positive in 12 of 24 pati ents with viral encephalitis. In animals the sensitivity of the assay was 87 percent and the specificity was 99 percent. Conclusions In pati ents with dementia, a positive immunoassay for the 14-3-3 brain protei n in cerebrospinal fluid strongly supports a diagnosis of Creutzfeldt- Jakob disease. This finding, however, does not support the use of the test in patients without clinically evident dementia.