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bioRxiv · 10.1101/562561

Stem cell derived human microglia transplanted in mouse brain to study genetic risk of Alzheimer's Disease

Mancuso, R.·Van Den Daele, J.·Fattorelli, N.·Wolfs, L.·Balusu, S.·Burton, O.·Sierksma, A.·Fourne, Y.·Poovathingal, S.·Arranz-Mendiguren, A.·Sala Frigerio, C.·Claes, C.·Serneels, L.·Theys, T.·Perry, V. H.·Verfaillie, C.·Fiers, M.·De Strooper, B.
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Abstract

Summary paragraphGenetics highlight the central role of microglia in Alzheimers disease but at least 36% of AD-risk genes lack good mouse orthologues. Here, we show that embryonic stem cell (ESC)-derived human microglia successfully engraft the mouse brain and recapitulate transcriptionally primary human microglia derived from human surgical samples. Upon exposure to oligomeric A{beta} a wide range of AD-risk genes are expressed that are not readily studied in current mouse models for AD. This work provides a unique humanized animal model that will allow elucidating the role of genetic risk in the pathogenesis of AD.

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Mancuso, R., Van Den Daele, J., Fattorelli, N., Wolfs, L., Balusu, S., Burton, O., Sierksma, A., Fourne, Y., Poovathingal, S., Arranz-Mendiguren, A., Sala Frigerio, C., Claes, C., Serneels, L., Theys, T., Perry, V. H., Verfaillie, C., Fiers, M., De Strooper, B.. 2019-02-27. Stem cell derived human microglia transplanted in mouse brain to study genetic risk of Alzheimer's Disease. https://doi.org/10.1101/562561

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