J.A. Blair

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.

The effect of lead on tetrahydrobiopterin metabolism. A possible mechanism for neurotoxicity

The use of low levels of lead in vivo in rats has been found to inhibit dihydropteridine reductase and cause an apparent increase in tetrahydrobiopterin biosynthesis. At higher dose levels inhibition of tetrahydrobiopterin biosynthesis has been observed. At low levels the disruption of tetrahydrobiopterin metabolism has been found to give an increase in the total level of biopterin derivatives but a movement away from the fully reduced form to the oxidised species in a manner consistent with dihydropteridine reductase inhibition. Lead has been found to inhibit dihydropteridine reductase in man.