Alzheimer's disease brain: alterations in RNA levels and in a ribonuclease-inhibitor complex.

A macromolecular alteration occurs at the posttranscriptional level in the Alzheimer's disease (AD) brain. Compared with age-matched controls, total cellular RNA and polyadenylated RNA were substantially reduced in the AD cortex with many neuritic plaques and neurofibrillary tangles. RNA changes are associated with a significant increase in alkaline ribonuclease activity due to an abnormality in the ribonuclease-inhibitor complex. The decrease in protein synthesis in the AD brain, previously observed in patients severely affected with AD, and in translation systems in vitro with AD cortical messenger RNA, may be partly related to an enzyme-inhibitor alteration that affects RNA levels and activity. Decreased protein synthesis therefore may contribute to the characteristic decline in certain neurotransmitter enzymes and to the loss of neurons in the AD brain.