Selective messenger RNA reduction in Alzheimer's disease

The relative abundance of 7 messenger RNAs extracted from Alzheimer and control neocortex were examined by Northern and quantitative dot blot analysis. The average yield of mRNA coding for NF-L, the 68-kDa moiety of neurofilament protein, was reduced to 27% of control when expressed as the percentage of total RNA or 14% when expressed per gram of neocortex. In contrast, the yields of 6 other messenger RNAs fell into two categories: those which were statistically significantly reduced to about 65% of control and those which were not reduced when expressed as percentage of total RNA. The anomalous low abundance of neuron specific NF-L mRNA, coding for the lowest molecular weight moiety of neurofilament proteins, in cerebral cortex of Alzheimer's disease cannot be adequately accounted for by a non-specific effect of brain damage, neuron cell loss or neurons with neurofibrillary degeneration. We speculate that this mRNA decrease is related to a functional deficit of gene expression in Alzheimer's disease, perhaps related to the non-random increase in chromatin compaction previously reported from this laboratory. The inability of neurons to maintain homeostatic amounts of NF-L transcription products may be linked to the accumulation of abnormal filamentous components characteristically associated with the diseased cytoskeleton.