Profiling Microglia From Alzheimer's Disease Donors and Non-demented Elderly in Acute Human Postmortem Cortical Tissue

Astrid M Alsema; Qiong Jiang; Laura Kracht; Emma Gerrits; Marissa L Dubbelaar; Anneke Miedema; Nieske Brouwer; Elly M Hol; Jinte Middeldorp; Roland van Dijk; Maya Woodbury; Astrid Wachter; Simon Xi; Thomas Möller; Knut P Biber; Susanne M Kooistra; Erik W G M Boddeke; Bart J L Eggen

doi:10.3389/fnmol.2020.00134

Profiling Microglia From Alzheimer's Disease Donors and Non-demented Elderly in Acute Human Postmortem Cortical Tissue

Front Mol Neurosci. 2020 Oct 28:13:134. doi: 10.3389/fnmol.2020.00134. eCollection 2020.

Authors

Astrid M Alsema¹, Qiong Jiang¹, Laura Kracht¹, Emma Gerrits¹, Marissa L Dubbelaar¹, Anneke Miedema¹, Nieske Brouwer¹, Elly M Hol², Jinte Middeldorp², Roland van Dijk², Maya Woodbury³, Astrid Wachter⁴, Simon Xi³, Thomas Möller³, Knut P Biber⁴, Susanne M Kooistra¹, Erik W G M Boddeke^{1

5}, Bart J L Eggen¹

Affiliations

¹ Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
² Department of Translational Neuroscience, UMC Utrecht Brain Centre, University Medical Centre Utrecht, University Utrecht, Utrecht, Netherlands.
³ Foundational Neuroscience Center, AbbVie Inc., Cambridge, MA, United States.
⁴ Neuroscience Discovery, AbbVie Deutschland GmbH and Co. KG, Ludwigshafen, Germany.
⁵ Department of Cellular and Molecular Medicine, Center for Healthy Ageing, University of Copenhagen, Copenhagen, Denmark.

Abstract

Microglia are the tissue-resident macrophages of the central nervous system (CNS). Recent studies based on bulk and single-cell RNA sequencing in mice indicate high relevance of microglia with respect to risk genes and neuro-inflammation in Alzheimer's disease (AD). Here, we investigated microglia transcriptomes at bulk and single-cell levels in non-demented elderly and AD donors using acute human postmortem cortical brain samples. We identified seven human microglial subpopulations with heterogeneity in gene expression. Notably, gene expression profiles and subcluster composition of microglia did not differ between AD donors and non-demented elderly in bulk RNA sequencing nor in single-cell sequencing.

Keywords: Alzheimer’s disease; barcoded Smart-seq2; human; microglia; single-cell RNA sequencing.