Transferrin receptors in the normal human hippocampus and in Alzheimer's disease.
Several lines of evidence suggest that aluminium may play a role in the pathogenesis of Alzheimer's disease (AD). The iron transport protein transferrin is the major transport protein for aluminium, and aluminium gains access to cells by means of a specific cell surface transferrin receptor. We have assessed the distribution of transferrin receptors in the normal and AD hippocampal formation using [3H]-transferrin ([3H]-Tf) binding and tritium film autoradiography, in order to assess the role of the transferrin receptor in AD. In normal brain, [3H]-Tf binding was highest in the pyramidal cell layers with CA2 > dentate gyrus granule cell layer > or = CA1 > CA3 > or = CA4 > subiculum > parahippocampal gyrus. In AD, significant reductions in [3H]-Tf binding were found in CA1, CA2 and CA4 pyramidal cell layers. The reduced [3H]-Tf binding in AD may, however, be due to poor pre-mortem agonal states which correlated with reduced [3H]-Tf binding. The discrepancy between the distribution of transferrin receptors in the hippocampus and those areas which are prone to the formation of senile plaques and neurofibrillary tangles suggests that if transferrin-mediated uptake of aluminium in AD/SDAT is significant in the pathogenesis of this disorder, it is not the only determinant of Alzheimer-type neuropathology.
Morris
C M
CM
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
Candy
J M
JM
Kerwin
J M
JM
Edwardson
J A
JA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001345:Autoradiography; D001665:Binding Sites; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D011990:Receptors, Transferrin / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D011990:Receptors, Transferrin