Graham LC, Harder JM, Soto I, de Vries WN, John SW, Howell GR. Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer's disease. Sci Rep. 2016 Feb 18;6:21568. PubMed.

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  1. The study is interesting, as it further confirms the importance of diets on markers related to AD neuropathology. It is focused on glial activation, which makes sense, as it replicates previous work showing high energy intake from fat increases GFAP (Buckman et al., 2015; Valdearcos et al., 2014; Julien et al., 2010). 

    The reported increase in TREM2 in microglia/monocytes is particularly novel and compelling, given recent publications in human CSF and animal models (Jay et al., 2015; Wang et al., 2015; St-Amour et al., 2015; Piccio et al., 2016). 

    Concerning the diet, I am not sure that a "true Western diet" is that well-defined, particularly when treating a mouse. Unfortunately, perhaps due to a lack of space, the authors do not describe the diet they have used very well (no detailed table of contents, at least in the PDF version I have). Thus it is hard to compare with previous work and to identify key dietary variables. 

    It would have been nice to look at tau pathology as well and to confirm peripheral metabolic impairments (glucose intolerance, insulin resistance, etc.) in the same animals.

    References:

    Buckman LB, Thompson MM, Lippert RN, Blackwell TS, Yull FE, Ellacott KL. Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice. Mol Metab. 2015 Jan;4(1):58-63. Epub 2014 Oct 16 PubMed.

    Valdearcos M, Robblee MM, Benjamin DI, Nomura DK, Xu AW, Koliwad SK. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 2014 Dec 24;9(6):2124-38. Epub 2014 Dec 11 PubMed.

    Julien C, Tremblay C, Phivilay A, Berthiaume L, Emond V, Julien P, Calon F. High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model. Neurobiol Aging. 2010 Sep;31(9):1516-31. Epub 2008 Oct 15 PubMed.

    Jay TR, Miller CM, Cheng PJ, Graham LC, Bemiller S, Broihier ML, Xu G, Margevicius D, Karlo JC, Sousa GL, Cotleur AC, Butovsky O, Bekris L, Staugaitis SM, Leverenz JB, Pimplikar SW, Landreth GE, Howell GR, Ransohoff RM, Lamb BT. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models. J Exp Med. 2015 Mar 9;212(3):287-95. Epub 2015 Mar 2 PubMed.

    Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, Gilfillan S, Krishnan GM, Sudhakar S, Zinselmeyer BH, Holtzman DM, Cirrito JR, Colonna M. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. 2015 Mar 12;160(6):1061-71. Epub 2015 Feb 26 PubMed.

    St-Amour I, Cicchetti F, Calon F. Immunotherapies in Alzheimer's disease: Too much, too little, too late or off-target?. Acta Neuropathol. 2016 Apr;131(4):481-504. Epub 2015 Dec 21 PubMed.

    Piccio L, Deming Y, Del-Águila JL, Ghezzi L, Holtzman DM, Fagan AM, Fenoglio C, Galimberti D, Borroni B, Cruchaga C. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol. 2016 Jun;131(6):925-33. Epub 2016 Jan 11 PubMed.

    View all comments by Frederic Calon

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  1. Microglial Marker TREM2 Rises in Early Alzheimer’s and on Western Diet