Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain

Topic: Brain proteins, microglia and lab models

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.

@article{farrar1990-1969510,
  author  = {Farrar, G. and Altmann, P. and Welch, S. and Wychrij, O. and Ghose, B. and Lejeune, J. and Corbett, J. and Prasher, V. and others},
  title   = {{Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain}},
  journal = {Lancet (London, England)},
  year    = {1990},
  doi     = {10.1016/0140-6736(90)90868-6},
  pmid    = {1969510},
  url     = {https://doi.org/10.1016/0140-6736(90)90868-6}
}

Key findings

• 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.

Why it matters

Plasma gallium-transferrin binding was significantly lower in people with Alzheimer's disease and Down syndrome than in controls, which the authors suggest could allow more unbound aluminium to enter the brain. This is an observational blood study and does not test whether reducing aluminium affects the disease.

Study details

• Effect size58.9%; 81.6%; 39.0%
• Evidence strengthLow

Read the original

• DOI: 10.1016/0140-6736(90)90868-6
• PubMed: 1969510
• Original source →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome Annals of Neurology · 1985-03-01 · usefulness score 56/100 · Down syndrome and Alzheimer's

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

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