Aluminium is neurotoxic and results in the proliferation of 100 A diameter filaments in the cytoplasm of certain neurons. The aluminium concentration for 7 normal human brains was 1-9 +/- 0-7 SD mug/g dry weight (n = 208 samples). The aluminium content of 585 areas sampled in 10 post-mortem cases of Alzheimer's disease ranging in age from 50 to 88 years, in which the diagnosis was based on the specific histological appearances, revealed an elevated aluminium content in some regions. A range of 0-4 - 107-0 mug/g was encountered and 28 per cent of all regions sampled had concentrations in excess of 4 mug/g. Five of 6 cerebral biopsies from patients with Alzheimer's disease also had elevated aluminium content. In 2 additional Alzheimer's brains with neurofibrillary degeneration restricted to certain anatomical areas, elevated aluminium content was found to be associated with neurofibrillary degeneration and not with senile plaques. Furthermore, elevated aluminium content in multiple cortical regions was not found in 2 vascular dementias of the elderly. While the cytotoxic concentration for human neurons is unknown, the cytotoxic concentration for cat's cerebral neurons appears to lie between 4 and 6 mug/g dry weight.

Nuclear and chromatin fractions were prepared from cerebral cortex of 34 human and 37 animal brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Compared to age-matched controls, aluminum content expressed per gram of DNA was significantly increased in nuclear and heterochromatin fractions in pre-senile Alzheimer's disease. In contrast nuclear preparations from brains of patients who had died with dialysis encephalopathy contained less aluminum than controls, although whole tissue concentrations were elevated ten to fifteen times above the control concentrations. Direct injection of aluminum into the cerebrospinal fluid of cats resulted in a progressive encephalopathy with neurofibrillary degeneration and increased intranuclear aluminum content. It is speculated that in Alzheimer's disease the normal blood-brain and cytoplasmic barriers for this neurotoxic metal are defective permitting aluminum to gain access to DNA-containing constitutents of the nuclei.

Chromatin samples were prepared from forty human brains. Chromatin was separated into a heavy heterochromatin fraction and two euchromatin fractions: intermediate euchromatin and light euchromatin. Employing a bacterial RNA polymerase as probe, only the euchromatin fractions were capable of RNA synthesis. In Control human brains, in brains of patients with dialysis dementia and in brains of elderly individuals without or with dementia of a type other than Alzheimer's disease, the euchromatin fractions accounted for about 75 per cent of the total DNA. In contrast, in brains of patients with advanced senile dementia or presenile dementia of the Alzheimer type, a wide range of euchromatin content was encountered with an average value of 55 per cent. Heterochromatization occurred in both neuron and glia enriched fractions suggesting that a major alteration in protein metabolism occurs in Alzheimer's disease.