Astrocyte- and Microglia-Specific Mitochondrial DNA Deletions Levels in Sporadic Alzheimer’s Disease

Article type: Research Article

Authors: Strobel, Sabrina^{a; j} | Grünblatt, Edna^{b; c; d} | Heinsen, Helmut^{e; f} | Riederer, Peter^{g; h} | Espach, Thomasⁱ | Meder, Michael^{a; j} | Monoranu, Camelia-Maria^{i; j; *}

Affiliations: [a] Institute of Pathology, University of Wuerzburg, Germany | [b] Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zürich, Switzerland | [c] Neuroscience Center Zurich, University of Zurich and the ETH Zurich, Zürich, Switzerland | [d] Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland | [e] Department of Psychiatry, Morphological Brain Research Unit, University of Wuerzburg, Wuerzburg, Germany | [f] Department of Pathology, University of São Paulo, São Paulo, Brazil | [g] Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany | [h] Department and Research Unit of Psychiatry, University of Southern Denmark Odense, Denmark | [i] Institute of Pathology, Department of Neuropathology, University of Wuerzburg, Germany | [j] Comprehensive Cancer Center (CCC) Mainfranken Wuerzburg, Germany

Correspondence: [*] Correspondence to: Camelia-Maria Monoranu, Institute of Pathology, Department of Neuropathology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany. Tel.: +49 931 31 81184; E-mail: camelia-maria.monoranu@uni-wuerzburg.de.

Abstract: Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer’s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage with an age-dependent accumulation. In a previous study, we analyzed mtDNA levels in diverse neuronal cell types in order to unravel the impact of oxidative stress in brains of AD patients. The aim of this study was to identify possible correlations between mtDNA deletion levels of selected astrocytes and microglia from three brain regions with different vulnerability to AD pathology and different stages of disease compared to controls. Our results reflect a higher vulnerability of hippocampal astrocytes and microglia to oxidative stress compared to other brain regions, such as cerebellum and brainstem.

Keywords: Alzheimer’s disease, astrocytes, brainstem, cerebellum, hippocampus, microglia, mitochondrial DNA, oxidative stress, selective vulnerability

DOI: 10.3233/JAD-180661

Journal: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 149-157, 2019