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Various coding genes representing multiple functional categories are downregulated in blood mononuclear cells (BMC) of patients with sporadic Alzheimer disease (AD). Noncoding microRNAs (miRNA) regulate gene expression by degrading messages or inhibiting translation. Using BMC as a paradigm for the study of systemic alterations in AD, we investigated(More)
Understanding complex diseases such as sporadic Alzheimer disease (AD) has been a major challenge. Unlike the familial forms of AD, the genetic and environmental risks factors identified for sporadic AD are extensive. MicroRNAs are one of the major noncoding RNAs that function as negative regulators to silence or suppress gene expression via translational(More)
Circulating microRNAs, present either in the cellular component, peripheral blood mononuclear cells (PBMC), or in cell-free plasma, have emerged as biomarkers for age-dependent systemic, disease-associated changes in many organs. Previously, we have shown that microRNA (miR)-34a is increased in circulating PBMC of Alzheimer's disease (AD) patients. In the(More)
The decline in cognitive robustness with aging can be attributed to complex genetic pathways involving many cellular dysfunctions, cumulative over time, precipitating in frailty and loss of wellness in the elderly brain. The size and health of the neuronal cell population determines cognitive robustness in mammals. A transgenic mouse model over-expressing(More)
In general, permanent growth arrest due to exhaustive cell replication can be induced prematurely by either stress or overexpression of selected oncogenes. In an attempt to examine key proteins involved in achieving premature senescence, and how they differ from those in serially passaged, replicatively exhausted cells, we used a novel proteomic profiling(More)
In replicative senescence, cells undergo permanent exit from cell cycle traverse; this is traditionally thought to occur at the end of a culture's in vitro life span, after serial passaging. In general, the checkpoint for replicative senescence is found at the G(1)/S border, controlled by the modulation of a battery of proteins, typified by gaining(More)
We evaluated pathomechanisms and systemic manifestations of Alzheimer disease (AD), an aging-related dementing neurodegenerative disorder, by expression profiling. Blood mononuclear cell (BMC) transcriptomes of sporadic AD subjects and aged-matched normal elderly controls (NEC) were compared using the human NIA microarray. Relative to the NEC samples, the(More)
MicroRNAs in blood samples have been identified as an important class of biomarkers, which can reflect physiological changes from cancer to brain dysfunction. In this report we identify concordant increases in levels of expression of miR-34a in brain and two components of mouse blood samples, peripheral blood mononuclear cells (PBMCs) and plasma, from 2 day(More)
MicroRNAs are a major category among the noncoding RNA fraction that negatively regulate gene expression at the post-transcriptional level, by either degrading the target messages or inhibiting their translation. MicroRNAs may be referred to as 'dimmer switches' of gene expression, because of their ability to repress gene expression without completely(More)
Functionally, adult stem cells not only participate in replication and differentiation to various cell lineages, but also may be involved in rescuing cells from apoptosis. Identifying functional factors secreted by stem cells, as well as their target cells, may advance our understanding of stem cells' multifaceted physiologic functions. Here, we report that(More)