Micro-RNA (miRNA) mediated regulation of messenger RNA (mRNA) complexity in the central nervous system (CNS) is emerging as a critical factor in the control of CNS-specific gene expression during development, plasticity, aging and disease. In these studies, miRNA array and Northern blot based tracking of specific miRNA abundances and decay kinetics in human neural (HN) cells in primary culture and in short post-mortem interval (PMI, approximately 1h) human brain tissues showed a limited stability and relatively short half-life ( approximately 1-3.5h) for specific brain-enriched miRNAs. In short PMI Alzheimer's disease (AD)-affected temporal lobe neocortex, miRNA-9, miRNA-125b and miRNA-146a were found to be significantly up-regulated, an effect that was not seen in several related neurological disorders. The results suggest (a) that unless specifically stabilized, certain brain-enriched miRNAs represent a rapidly executed signaling system employing highly transient effectors of CNS gene expression, and (b) that in AD temporal lobe neocortex specific brain miRNAs are significantly up-regulated in abundance and strongly correlate with the presence of AD-type neuropatholgical change.