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Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia

Abstract

In Alzheimer's disease, microglia cluster around β-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque formation and maintenance nor amyloid-associated neuritic dystrophy depended on the presence of microglia.

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Figure 1: Virtually complete microglia ablation in icv GCV-treated APPPS1; TK mice does not alter Aβ plaque load.
Figure 2: Amyloid plaque formation in microglia-ablated APPPS1; TK mice.

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Acknowledgements

This work was supported by grants to M.J. (BMBF-01GI0705), F.L.H. (SFB-TR43, Exc 25 and National Institutes of Neurological Disorders and Stroke R01 NS046006) and P.M.M. (US National Institutes of Health AG017617 and NS045205).

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S.A.G., T.B., S.A.K., J.O., R.R., T.E., P.M.M. and H.W. performed the icv experiments. R.E.K., S.P. and G.W. carried out the oral treatment experiments. A.A., M.S. and S.G. provided mice and/or advice. Experimental design and manuscript preparation were mainly carried out by F.L.H. and M.J.

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Correspondence to Frank L Heppner or Mathias Jucker.

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Supplementary Figures 1–5 and Supplementary Methods (PDF 3074 kb)

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Grathwohl, S., Kälin, R., Bolmont, T. et al. Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia. Nat Neurosci 12, 1361–1363 (2009). https://doi.org/10.1038/nn.2432

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