Characterization of messenger RNA from the cerebral cortex of control and Alzheimer-afflicted brain.

A detailed comparative study of RNA transcripts isolated from the neocortex of control and Alzheimer postmortem brains was made to determine whether morphological changes in the chromatin of Alzheimer neurons and glia, which we reported earlier, are accompanied by changes in the products of transcription. A number of parameters were determined including the yields of total and mRNA per gram of tissue, the relative proportions of polyadenylated [poly(A)+] mRNA in the total RNA, the size distribution of the transcripts and the length of their poly(A) tails, and the nature of their in vitro translation products. The levels of endogenous RNase activity were also measured. The effect of the agonal process on the transcript complement was examined by Northern blotting of a cloned human heat-shock cDNA to total human brain RNA. Our results reveal that the yields of total RNA, unadenylated mRNA, and poly(A) tail lengths from Alzheimer neocortex samples do not differ significantly from those of control and non-Alzheimer dementia neocortex. On the other hand we find a significant reduction in the levels and proportion of poly(A)+ mRNA in the Alzheimer samples as compared to control brain samples. Quantitative rather than qualitative differences were observed in the in vitro translation products when programmed with control and Alzheimer mRNA. No differences were found in the levels of RNase activity between control and Alzheimer samples. Heat-shock mRNA transcripts were detected in brain samples from patients in whom fever was associated with death. The direct correlation of reduced poly(A)+ mRNA and chromatin condensation in Alzheimer neocortex suggests a cause-and-effect relationship. Whether all transcribed genes are affected or only a specific subset has yet to be determined.