Cytoskeletal messenger RNA stability in human neocortex: studies in normal aging and in Alzheimer's disease

Total RNA was extracted from human brain temporal and parietotemporal neocortical grey matter with postmortem intervals (PMI) of up to 13.5 hours. The integrity and rank abundance of heterogeneous nuclear RNA (HnRNA) and messenger RNA (mRNA) were analyzed by Northern gel dot blot hybridization with specific cloned probes of neurobiological interest: the RNA messages for four cytoskeletal components including glial fibrillary acidic protein (GFAP), alpha-tubulin, beta-actin and the human neurofilament light chain (HNF-L) genomic sequence, the Alu repetitive element, the scrapie prion PrP DNA probe and the chromatin condensing agent linker histone H1(0) genomic probe. Our observations indicate that for the cytoskeletal RNA messages studied here: (1) short postmortem intervals (of up to 4.5 hours) had only small effects upon RNA quality in these neocortices, (2) GFAP and HNF-L transcripts were represented at relatively high levels in the cerebral neocortex and (3) each RNA species in normal human brain had both unique and characteristic intracellular levels of abundance and decay kinetics. In the pathological condition, Alzheimer's disease (AD), cells of the temporal and parietotemporal neocortices of afflicted brains showed selective reductions in cytoskeletal RNA pool size which are not attributable to RNA transcript stability.