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Kang SS, Ebbert MT, Baker KE, Cook C, Wang X, Sens JP, Kocher JP, Petrucelli L, Fryer JD. Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau. J Exp Med. 2018 Sep 3;215(9):2235-2245. Epub 2018 Aug 6 PubMed.
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This is an innovative study using the RiboTag technology to capture transcripts while they are being translated, potentially avoiding unwanted bias when microglia are isolated for profiling. The authors have generated publically accessible translational profiling data in models of amyloidosis, tauopathy, and aging. More interesting, they found that although ApoE is known to be an astrocytic gene in the brain, the absolute abundance of ApoE under basal conditions is among the top 1 percent of all transcripts expressed in microglia, while further upregulated in aging, amyloidosis, and tauopathy. Such observations suggest that ApoE may have a primary role in microglia under both physiological and pathological conditions. This also opens up a whole new possibility of exploring whether ApoE function in microglia contributes to its risk effects on AD, a topic that has received increasing attention in recent scientific meetings.View all comments by Guojun Bu
Picower Institute of MIT
I think the RiboTag system is an elegant approach to profile ribosome-associated transcripts in a minimally invasive fashion as demonstrated by Kang et al. and other labs who have successfully applied the approach to study diverse microglia phenotypes (Ayata et al., 2018; Haimon et al., 2018).
The difference in the response of male and female microglia to challenge reported by Kang et al. is in line with previous studies reporting that gender may markedly affect the phenotype of microglia (Thion et al., 2018; Rahimian et al., 2018). Kang et al. also find that aging, a well-known risk factor for AD, increases the expression of APOE in microglia more so in female than in male mice. It would be interesting to know if this has any implication in the higher incidence of AD in women than in men. Together, these findings inform about a sexual dimorphism in a cell type that is known to play an important role in many neurodegenerative disorders.
Ayata P, Badimon A, Strasburger HJ, Duff MK, Montgomery SE, Loh YE, Ebert A, Pimenova AA, Ramirez BR, Chan AT, Sullivan JM, Purushothaman I, Scarpa JR, Goate AM, Busslinger M, Shen L, Losic B, Schaefer A. Epigenetic regulation of brain region-specific microglia clearance activity. Nat Neurosci. 2018 Aug;21(8):1049-1060. Epub 2018 Jul 23 PubMed.
Haimon Z, Volaski A, Orthgiess J, Boura-Halfon S, Varol D, Shemer A, Yona S, Zuckerman B, David E, Chappell-Maor L, Bechmann I, Gericke M, Ulitsky I, Jung S. Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies. Nat Immunol. 2018 Jun;19(6):636-644. Epub 2018 May 18 PubMed.
Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JK, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell. 2018 Jan 25;172(3):500-516.e16. Epub 2017 Dec 21 PubMed.
Rahimian R, Cordeau P Jr, Kriz J. Brain Response to Injuries: When Microglia Go Sexist. Neuroscience. 2018 Mar 8; PubMed.View all comments by Li-Huei Tsai
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