No abstract

SUMMARY In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of largd cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex.

1. The soluble and insoluble fractions of eight species of bacteria were separated by centrifuging the material obtained after disintegrating the cells by shaking with glass beads.2. The insoluble material, believed to be at least mainly derived from the cell wall, accounted in most cases for about half of the dry weight of the cell.3. Estimations were performed on both fractions for ash, nitrogen, phosphorus, hexose, pentose, deoxypentose and nucleic acid, the last being determined spectroscopically.4. Wide variations were found among different organisms but certain regularities were observed. Notably, nucleic acid was confined to the soluble fraction, which was also much richer in phosphorus, pentose and deoxypentose.5. Concepts ofthe bacterial cell wall are discussed in the light of these findings.We are deeply indebted to Prof. R. A. Morton, F.R.S., for his interest and encouragement throughout; to the Ministry of Education for a grant to one of us (W. R.F.) under the Further Education and Training Scheme; and to the Medical Research Council for financial assistance in the provision of materials and equipment.

The concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was measured in the cerebral cortex obtained at diagnostic craniotomy from 10 patients with Alzheimer's disease of 3 yrs mean duration and 6 patients with other causes of dementia, and from 31 subjects undergoing other neurosurgical procedures (for which removal of apparently normal tissue was necessary). GABA content of 5 areas of the cerebral cortex and the cerebellar cortex was measured postmortem in the brains of 23 Alzheimer and 19 control subjects and 5 patients with other causes of dementia. Fourteen of these specimens, including 7 from patients with Alzheimer's disease of 8 yrs mean duration, were obtained within 3 h of death. These were processed in a similar manner to the neurosurgical specimens and are regarded also as fresh tissue samples. The remaining 33 specimens are regarded as conventional postmortem samples as the mean interval of death to autopsy was 21 h. GABA concentration in conventional autopsy specimens from Alzheimer subjects was not reduced as compared with controls in either cingulate or cerebellar cortex. In the inferior parietal cortex, agonal status confounded this comparison. The concentration was reduced in superior parietal, frontal and temporal cortex but there is a possibility that agonal state also confounded these comparisons. There was no deficit in GABA concentration in fresh cortical tissue from Alzheimer patients except for the temporal lobe from autopsy specimens. The content of somatostatin-like immunoreactivity was, like GABA, found to be comparable to control in some groups of Alzheimer specimens. It is argued that the deficits in autopsy samples and lack of change in surgical specimens is likely to be due to the duration of illness at the time of sampling. Losses of choline acetyltransferase activity were observed in all groups of Alzheimer specimens in all areas of brain studied. The data are consistent with other results which suggest that cholinergic under-activity is most closely related to the clinical course of Alzheimer's disease.