Laser microprobe analysis of brain aluminum in Alzheimer' disease

Aluminum (Al) levels were measured in the cytoplasm and nucleus of 241 neurofibrillary tangle (NFT)‐bearing neurons, in 217 NFT‐free neurons and adjacent neuropil from 7 autopsy‐confirmed Alzheimer's disease (AD) patients, and in 316 normal neurons from 5 control subjects, by laser micriprobe mass spectrometry. Grand mean Al levels (dry weight basis) in AD samples were 2.93 ± 1.24 μg/gm for NFT‐bearing neuron cytoplasm, 3.54 ± 1.39 μg/gm for NFT‐bearing neuron nuclei, 2.31 ± 1.09 μg/gm for NFT‐free neuron cytoplasm, and 3.23 ± 1.09μg/gm for NFT‐free neuron nuclei. Control values were 1.85 ± 0.78 μg/gm for cytoplasm and 2.01 ± 0.93 μg/gm for nuclei. The differences between corresponding regions of AD NFT‐bearing, AD NFT‐free, and control neurons were not significant (p > 0.05, analysis of variance). Al levels in neuropil were identical for AD and control samples at 2.16 ± 0.93 μg/gm. In contrast to some literature reports, we found very few (<2.5%) extremely high Al values (>20μg/gm, dry weight) on a cellular basis in AD samples. AD neurons did exhibit a higher number of Al values (9.6−14.3%) that were >sgrave; above the corresponding control means, than did control neurons (1.3–1.6%), indicating that small elevations of Al may exist in patients with AD. Our data suggest that any Al accumulation in patients with AD is small and generalized in both NFT‐free and NFT‐bearing neurons and that analyses of large bulk brain samples are likely to have AD/control differences masked by the large amount of unaffected neuropil sampled.