Distribution of transferrin and ferritin binding in normal and multiple sclerotic human brains

Delivery of iran to the brain traditionally has been considered the respons ibility of transferrin. However, transferrin receptors in brain are located primarily within gray matter areas rather than in the iron rich white matt er tracts. In this report we present the first demonstration of ferritin bi nding sites in human brain and provide evidence that these binding sites ar e primarily in white matter tracts. This distribution of ferritin binding i s opposite of that seen for the distribution of the transferrin receptor in normal adult human brain. Ferritin binds to human brain tissue in a compet itive and saturable manner with a dissociation constant of 0.35 nM and a bi nding site density of 116.7 fmol/mg protein. In brain tissue from multiple sclerotic (NS) patients the normal pattern of transferrin and ferritin bind ing distributions is disrupted. Ferritin binding is absent in the lesion it self and in the immediate periplaque region within the white matter but ret urns to normal as the distance from the lesion becomes greater; rn direct c ontrast to ferritin binding, transferrin binding in the MS tissue is presen t in the white matter tracts, but only in the periplaque region. The peripl aque region also contains transferrin receptor positive cells (as determine d by immunocytochemistry) morphologically consistent with oligodendrocytes. Gray matter binding of transferrin in MS patients appears normal. These da ta provide the initial evidence of ferritin binding in human brain, address the enigma of the apparent absence of an iron delivery system to the iron- rich white matter, and suggest loss of ferritin binding is involved in or i s a consequence of demyelination associated with MS. (C) 1998 Elsevier Scie nce B.V. All rights reserved.