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

Renzo Mancuso; Johanna Van Den Daele; Nicola Fattorelli; Leen Wolfs; Sriram Balusu; Oliver T. Burton; Adrian Liston; Annerieke S. R. Sierksma; Yannick Fourne; Suresh Kumar Poovathingal; Amaia M. Arranz; Carlo Sala Frigerio; Christel Claes; Lutgarde Serneels; Tom Theys; Victor Hugh Perry; Catherine M. Verfaillie; Mark W. E. J. Fiers; Bart De Strooper

doi:10.1038/s41593-019-0525-x

NeuroscienceNature NeuroscienceOct 28, 2019

Peer-reviewed journal article

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

Renzo Mancuso iD, Johanna Van Den Daele iD, Nicola Fattorelli iD, Leen Wolfs iD, Sriram Balusu iD, Oliver T. Burton iD, Adrian Liston iD, Annerieke S. R. Sierksma iD, Yannick Fourne, Suresh Kumar Poovathingal iD, Amaia M. Arranz iD, Carlo Sala Frigerio iD, Christel Claes iD, Lutgarde Serneels iD, Tom Theys iD, Victor Hugh Perry iD, Catherine M. Verfaillie iD, Mark W. E. J. Fiers iD, Bart De Strooper iD

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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