BETA-AMYLOID PRECURSOR PROTEIN ISOFORMS SHOW CORRELATIONS WITH NEURONS BUT NOT WITH GLIA OF DEMENTED SUBJECTS

Post-mortem cerebral cortex from 15 demented patients was specially co llected to minimise autolysis and two membrane fractions and one solub le fraction were quantitatively examined for the major species of beta -amyloid precursor protein (APP) of high apparent molecular mass (grea ter than or equal to 80 kDa) together with the major mRNA species enco ding APP isoforms. The number of pyramidal neurones and astrocytes, pu tative biochemical indices of interneurones and pyramidal neurones, an d choline acetyl transferase activity were also determined. Multiple r egression analysis has been used to investigate intercorrelations of A PP species with biochemical and morphometric measures, free of any eff ects of confounding demographic variables. Subjects with Alzheimer's d isease showed a loss of cholinergic activity and D-aspartate uptake co mpared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell number s were positively correlated with mRNA for APP(695). APP in the solubl e fraction showed a negative correlation with pyramidal cell numbers a nd cholinergic activity. These results indicate that neurones within t he cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and choline rgic activity.