Systems analysis of blood transcriptomes in dementia patients reveals an innate immune response shared across disorders

Nachun, D.; Ramos, E. M.; Karydas, A.; Dokuru, D.; Gao, F.; Yang, Z.; Van Berlo, V.; Sears, R. L.; Kramer, J.; Boxer, A. L.; Rosen, H. H.; Miller, B. L.; Coppola, G.

doi:10.1101/2019.12.13.875112

bioRxiv · 10.1101/2019.12.13.875112

Systems analysis of blood transcriptomes in dementia patients reveals an innate immune response shared across disorders

Nachun, D.·Ramos, E. M.·Karydas, A.·Dokuru, D.·Gao, F.·Yang, Z.·Van Berlo, V.·Sears, R. L.·Kramer, J.·Boxer, A. L.·Rosen, H. H.·Miller, B. L.·Coppola, G.

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Abstract

The role of peripheral inflammation in dementia is an important but complex topic. We present here the largest cohort of peripheral blood gene expression data ever assembled from patients with dementia and matching controls. Importantly, this cohort includes individuals from a diverse set of dementia disorders, including Alzheimers Disease (AD), mild cognitive impairment (MCI), and multiple disorders within the frontotemporal dementia (FTD) spectrum. We found strong transcriptional evidence of an innate immune inflammatory response, mediated by monocytes and neutrophils, in AD, MCI, and two FTD subtypes, PSP and nfvPPA. This transcriptional inflammatory response is enriched for genetic risk for AD, in part because it is also enriched for microglial genes, which have previously been implicated in AD risk. Finally, we show that this transcriptional response is strongly enriched for binding of the transcription factors PU.1 and RELA, which have previously been linked to AD risk and progression.

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Nachun, D., Ramos, E. M., Karydas, A., Dokuru, D., Gao, F., Yang, Z., Van Berlo, V., Sears, R. L., Kramer, J., Boxer, A. L., Rosen, H. H., Miller, B. L., Coppola, G.. 2019-12-13. Systems analysis of blood transcriptomes in dementia patients reveals an innate immune response shared across disorders. https://doi.org/10.1101/2019.12.13.875112

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