. An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem. 2008 Nov 14;283(46):31315-22. PubMed.

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  1. This is an interesting follow-up study from Lukiw’s group on the possible role of microRNAs in AD. Here, the authors identify a novel regulatory pathway (NFκB > miR-146a > complement factor H) potentially involved in the inflammation response in AD brain. Hence, apart from modulating directly BACE1 and Aβ levels (as shown by us and Peter Nelson’s group), the microRNA network is emerging as a potential important contributor to AD pathology.

    The findings presented in this paper originate from the observation that miR-146a levels are elevated in AD brain. Whether these changes in miR-146a are confirmed in an independent set of patient samples remains to be seen. Indeed, current studies in humans suggest no or minimal overlap in changes in microRNA expression profiles in AD brain. While this does not exclude a role for microRNAs in neurodegeneration—which is clearly supported by studies in animals—it is important to take into consideration the experimental variables which may explain these differences. An important issue when interpreting alterations in microRNA expression is also the cause or consequence question. Here, the authors could induce an increase in miR-146a levels in cultured human neuronal (and glial) cells treated with synthetic Aβ and IL-1β, thus suggesting a detrimental feedback loop between Aβ and inflammation.

    In sum, it’s becoming increasingly apparent that loss of the fine genetic regulation by the microRNA network, in combination with the increased Aβ load in the aging neurons, could provide a scenario for the severe neurodegeneration observed in AD brain.