The big picture: Alzheimer’s transcriptome, insulin phosphoproteome

For all you genomics and systems-level junkies out there, here are two very juicy genome-scale (in one case, proteome-scale) studies of two very different aging-related phenomena: From Miller et al., we have a systems-level analysis of gene expression in both Alzheimer’s disease (AD) and normal aging. The authors use the transcriptional data in conjunction with genome annotation to identify pathways that are coherently regulated, either by neurodegenerative changes or age-related decline. Since the authors focus on brain tissue rather than the more easily accessible (or biopsy-able) parts of the body, these findings will be more relevant to understanding the pathology of AD than to its diagnosis. Hence, this approach is complementary to recent studies aimed at identifying proteins that are differentially expressed in the blood of AD patients and can therefore be used as diagnostic biomarkers for the disease.

Meanwhile, Krüger et al. have used mass spectrometry to characterize the tyrosine phosphoproteome of the insulin signaling pathway — in other words, they looked for proteins that are differentially tyrosine-phosphorylated as a result of insulin action. In addition to rounding up proteins already known to be involved, they also report the identification of several novel effectors of insulin signaling. The technique appears quite robust, and I look forward to seeing this methodology extended to other aging-related signaling networks (such as the closely related IGF-1 pathway).


One comment

  1. no new clues on mitos’ involvement: “Mitochondria and synaptic dysfunction in AD
    The unsupervised network analysis of AD provides an interesting perspective on mitochondrial and synaptic dysfunction. Because both mitochondria and synapses fail with increasing age and disease progression, and because oxidative damage is one of the earliest pathological changes seen in AD (Nunomura et al., 2001Go), it has been suggested that mitochondrial dysfunction is the underlying cause for disease pathology (Beal, 2005Go; Lin and Beal, 2006Go). Although the expression profiles for the mitochondrial and synaptic modules look relatively similar, they can clearly be separated by their PCs (Fig. 2, the brown point falls in the “metabolic group,” not the “synaptic group”). This separation suggests that mitochondrial and synaptic genes are likely involved in distinct, yet related processes. Such results cannot determine causal relationships, yet the idea that mitochondrial dysfunction may in part lead to neuroplasticity failure, as suggested by Beal et al. (Beal, 2005Go; Lin and Beal, 2006Go), remains intriguing.”

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