Abnormal Proteins in the Cerebrospinal Fluid of Patients with Creutzfeldt–Jakob Disease

We studied more than 300 cerebrospinal fluid proteins from 21 patients with Creutzfeldt–Jakob disease. We also examined cerebrospinal fluid from 100 normal controls and more than 400 patients with various neurologic disorders other than Creutzfeldt–Jakob disease. Four abnormal proteins that were identified in the patients with Creutzfeldt–Jakob disease were absent in the normal persons. Two of these proteins (Mr [relative molecular mass], 40,000; pl [isoelectric point], 5.7 and Mr 40,000; pl 5.9) were also present in some patients with multiple sclerosis, herpes simplex encephalitis, schizophrenia, Parkinson's disease, or Guillain–Barré or Behçet's syndrome. Two proteins (Mr 26,000; pl 5.2 and Mr 29,000; pl 5.1) were present in all patients with Creutzfeldt–Jakob disease and in 5 of 10 patients with herpes simplex encephalitis, but in none of the other control groups. A subsequent blinded study of these cerebrospinal fluid proteins from patients with Creutzfeldt–Jakob disease, Alzheimer's disease, Huntington's disease, multiinfarct dementia, parkinsonism dementia of Guam, or the specific dementia of the acquired immunodeficiency syndrome resulted in the ability to distinguish all cases of Creutzfeldt–Jakob disease from the other types of dementia. Although the identity and origin of the abnormal spinal fluid proteins are not yet known, these preliminary results suggest that their presence may help in the diagnosis of Creutzfeldt–Jakob disease. (N Engl J Med 1986; 315: 279–83.) CREUTZFELDT–JAKOB disease is a fatal, transmissible form of dementia. 1 The infectious agent is referred to as an "unconventional" virus 2 or prion. 3 There is no specific immune response to the infectious particle in the brain, 4 serum, 5 or cerebrospinal fluid 6 of patients with the disease. Antemortem diagnosis must be made by biopsy of affected brain tissue. 7 Detection of scrapie-associated fibrils by negative-stain electron microscopy 8 and of "prion" proteins by electrophoresis 9 10 11 of extracts from brain tissue provide additional information that is useful for diagnosis. 12 A biopsy of brain tissue is not performed until late in the course of the disease because of the . . .