There are other notable differences between the protein fractions of CSF and plasma. The CSF always contains a prealbumin fraction and the plasma does not. Although derived from plasma, this fraction, for an unknown reason, concentrates in the CSF, and its level is greater in ventricular than in lumbar CSF, perhaps because of its concentration by choroidal cells. Also, tau (also identified as beta2-transferrin) is detected only in the CSF and not in other fluids; its concentration is higher in the ventricular than in the spinal fluid. The concentration of tau protein and in particular the ratio of tau to beta-amyloid, has found use in the diagnosis of Alzheimer disease, as discussed in Chap. 38. At present only a few of these proteins are known to be associated with specific diseases of the nervous system. The most important is IgG, which may exceed 12 percent of the total CSF protein in diseases such as multiple sclerosis, neurosyphilis, subacute sclerosing panencephalitis and other chronic viral meningoencephalitides. The serum IgG is not correspondingly increased, which means that this immune globulin originates in (or perhaps is preferentially transported into) the nervous system. However, an elevation of serum gamma globulin—as occurs in cirrhosis, sarcoidosis, myxedema, and multiple myeloma—will be accompanied by a rise in the CSF globulin. Therefore, in patients with an elevated CSF gamma globulin, it is necessary to determine the electrophoretic pattern of the serum proteins as well. Certain qualitative changes in the CSF immunoglobulin pattern, particularly the demonstration of several discrete (oligoclonal) electrophoretic “bands,” each representing a specific immune globulin, and the ratio of IgG to total protein, are of special diagnostic importance in multiple sclerosis, as discussed in Chap. 36.
The albumin fraction of the CSF increases in a wide variety of central nervous system (CNS) and craniospinal nerve root diseases that increase the permeability of the blood–CSF barrier, but no specific clinical correlations can be drawn. Certain enzymes that originate in the brain, especially the brain-derived fraction of creatine kinase (CK-BB) but also enolase and neopterin, are found in the CSF after stroke, global ischemic hypoxia, or trauma, and have been used as markers of brain damage in experimental work. Other special markers such as elevation of the 14-3-3 protein, which has some diagnostic significance in prion disease, β2-microglobulin in meningeal lymphomatosis, neuron-specific enolase in traumatic and other severe brain injuries, and alpha fetoprotein in embryonal tumors of the brain, may be useful in specialized circumstances.