Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain.
The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.
Farrar
G
G
Division of Biology, University of Aston, Birmingham, UK.
Altmann
P
P
Welch
S
S
Wychrij
O
O
Ghose
B
B
Lejeune
J
J
Corbett
J
J
Prasher
V
V
Blair
J A
JA
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000378:metabolism*; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D015140:Dementia, Vascular / Q000097:blood / Q000378:metabolism*; D004314:Down Syndrome / Q000097:blood / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D005260:Female; D005710:Gallium Radioisotopes / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014168:Transferrin / Q000032:analysis / Q000378:metabolism*
D005710:Gallium Radioisotopes; D014168:Transferrin; D000535:Aluminum