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.