INPP5D limits plaque formation and glial reactivity in the APP/PS1 mouse model of Alzheimer's disease

Castranio, E. L.; Hasel, P.; Haure-Mirande, J.-V.; Ramirez, A. V.; Hamilton, B. W.; Kim, R. D.; Wang, M.; Zhang, B.; Gandy, S.; Liddelow, S. A.; Ehrlich, M. E.

doi:10.1101/2022.04.29.490076

bioRxiv · 10.1101/2022.04.29.490076

INPP5D limits plaque formation and glial reactivity in the APP/PS1 mouse model of Alzheimer's disease

Castranio, E. L.·Hasel, P.·Haure-Mirande, J.-V.·Ramirez, A. V.·Hamilton, B. W.·Kim, R. D.·Wang, M.·Zhang, B.·Gandy, S.·Liddelow, S. A.·Ehrlich, M. E.

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Abstract

The dual specificity lipid/protein phosphatase SHIP1 (encoded by the INPP5D gene) is enriched in myeloid cells. Single nucleotide polymorphisms (SNPs) in INPP5D coding and non-coding regions impact risk for developing late onset sporadic Alzheimers disease (LOAD). We present pathological analyses with spatial transcriptomics of mice with tamoxifen-sensitive microglial knockdown of Inpp5d and show exacerbated plaque pathology, plaque-associated microglial density, and altered gene expression around plaques, suggesting novel markers for plaque-associated reactive microglia.

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Castranio, E. L., Hasel, P., Haure-Mirande, J.-V., Ramirez, A. V., Hamilton, B. W., Kim, R. D., Wang, M., Zhang, B., Gandy, S., Liddelow, S. A., Ehrlich, M. E.. 2022-04-30. INPP5D limits plaque formation and glial reactivity in the APP/PS1 mouse model of Alzheimer's disease. https://doi.org/10.1101/2022.04.29.490076

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