All organs including the brain contain iron, and the proteins involved
in iron uptake (transferrin and transferrin receptor) and intracellul
ar storage (ferritin). However, because the brain resides behind a bar
rier and has a heterogeneous population of cells, there are aspects of
its iron management that are unique. Iron management, the timely deli
very of appropriate amounts of iron, is crucial to normal brain develo
pment and function. Mismanagement of cellular iron can result not only
in decreased metabolic activity but increased vulnerability to oxidat
ive damage. There is regional specificity in cell deposition of iron a
nd the iron regulatory proteins. However, the sequestration of iron in
the brain seems primarily the responsibility of oligodendrocytes, as
these cells contain most of the stainable iron in the brain. Transferr
in, the iron-mobilizing protein, is also found predominantly in these
cells. The transferrin receptor is abundantly expressed on blood vesse
ls, large neurons in the cortex, striatum, and hippocampus, and is als
o present on oligodendrocytes and astrocytes. Ferritin, the intracellu
lar iron storage protein, consists of 2 subunits which are functionall
y distinct, and we provide evidence in this report that the cellular d
istribution of the ferritin subunits is also distinct. In addition, ch
anges in the cellular distribution of iron and its associated regulato
ry proteins occur in Alzheimer's disease. Neuritic plaques contain rel
atively large amounts of stainable iron, and the surrounding cells rob
ustly immunostain for ferritin and the transferrin receptor. Analysis
of the cellular distribution of iron indicates the different levels of
requirement of iron in the brain by different cell types and should u
ltimately elucidate how cells acquire and maintain this essential comp
onent of oxidative metabolism. In addition, changes in the ability of
cells to deliver and manage iron may provide insight into altered meta
bolic activity with age and disease as well as identify cell populatio
ns at risk for iron-induced oxidative stress.