Gastrointestinal absorption of aluminum is increased in Down's syndrome.

Individuals with Down's Syndrome (DS) develop the neuropathological features of senile dementia of the Alzheimer's type (SDAT) by early middle age. Because of recent evidence that gastrointestinal (GI) aluminum (Al) absorption is increased in patients with SDAT, and that Al may contribute to associated neuropathological changes, we have investigated the GI uptake of Al in patients with DS by two methods. The first measured the absorption of 27Al at concentrations associated with antacid use, in the presence of citrate, using atomic absorption spectrometry. There was no difference between basal blood concentrations of 27Al in 15 DS subjects (36-46 years) and 15 age-matched controls. The mean increase in 27Al blood concentrations 60 minutes after the dose of Al was four times greater in the DS group than in controls (p < 0.001). The second measured GI absorption of 26Al under normal dietary conditions using accelerator mass spectrometry. With 26Al the mean Al absorption in DS subjects (n = 5) exceeded that of controls (n = 4) by a factor of 6 (p < 0.02). Although the mechanisms of enhanced absorption are unknown, the data indicate that similar abnormalities in the GI handling of Al occur in both SDAT and DS suggesting that it may be advisable to minimize dietary exposure to Al in subjects at risk of developing Alzheimer-type pathology.

Uptake of 26-Al and 67-Ga into brain and other tissues of normal and hypotransferrinaemic mice.

Aluminium uptake from blood into tissues of control and homozygous hypotransferrinaemic (hpx/hpx) mice, following continuous intravenous infusion of 26Al and 67Ga, has been compared with that of gallium, a proposed tracer for aluminium. 26Al uptake into tissues of control (hpx/+ and +/+) mice occurred in the order (expressed as a space): bone 464.7 ml 100 g-1; renal cortex 102.9 ml 100 g-1; liver 13.0 ml 100 g-1; spleen 8.4 ml 100 g-1 and brain 0.8 ml 100 g-1. 67Ga uptakes were similar in liver, spleen and brain, but smaller in the renal cortex and bone, at one-third and one-fifth of the values for 26Al, respectively. In the hypotransferrinaemic mice, uptake of 67Ga into all tissues was increased, especially in renal cortex (ninefold) and bone (twentyfold) as compared with the controls. Increases in 67Ga uptakes into cerebral hemisphere, cerebellum and brain stem of the hypotransferrinaemic mice were 3.8, 4.2 and 2.8 fold, respectively. 26Al uptake into tissues of the hypotransferrinaemic mice was similar to control values except in bone where it was three times greater. Pre-treatment of control animals with the anti-transferrin receptor antibody, RI7 208, enhanced 67Ga uptake in all tissues, the effect being greatest in renal cortex (tenfold) and bone (ninefold). 67Ga uptakes into cerebral hemisphere, cerebellum and brain stem in the mice pre-treated with RI7 208 were 6.4, 6 and 10 times greater than in untreated mice, respectively. No influence of antibody on 26AI uptake into mouse tissues was observed except in spleen where it was three times greater than in untreated mice. Hence, transport of aluminium and gallium into mouse tissues is not similar under all conditions. Non-transferrin mediated transport of each metal can occur into all tissues, especially in renal cortex and bone, where gallium may be a suitable marker for aluminium.

Effect of silicon on gastrointestinal absorption of aluminium.

The reported geographical association between Alzheimer's disease and levels of aluminium (Al) in water supplies may reflect the inverse relation between Al and silicon (Si) concentrations in water, and the potential for Si to reduce the bioavailability of the metal. We tested this hypothesis using isotopic 26Al tracer administered orally to five healthy volunteers in the presence and absence of Si. Dissolved Si, at a concentration found in some water supplies (100 mumol/L), reduced the peak plasma 26Al concentration to 15% of the value obtained in the absence of Si. The results indicate that dissolved Si is an important factor in limiting the absorption of dietary Al.