Age-Dependent Decrease of Mitochondrial Complex II Activity in a Familial Mouse Model for Alzheimer’s Disease

Article type: Short Communication

Authors: Emmerzaal, Tim L.^a | Rodenburg, Richard J.^b | Tanila, Heikki^c | Verweij, Vivienne^a | Kiliaan, Amanda J.^a | Kozicz, Tamas^{a; d; *}

Affiliations: [a] Department of Anatomy, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegen, The Netherlands | [b] Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands | [c] A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland | [d] Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA

Correspondence: [*] Correspondence to: Tamas Kozicz, Department of Clinical Genomics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail: [email protected].

Abstract: Alzheimer’s disease (AD) is a severe neurodegenerative disorder for which the exact etiology is largely unknown. An increasingly recognized and investigated notion is the pathogenic role of mitochondrial dysfunction in AD. We assessed mitochondrial oxidative-phosphorylation (OXPHOS) enzyme activities in the APPswe/PS1ΔE9 mouse model from 4.5 to 14 months of age. We show an age-dependent decrease in mitochondrial complex-II activity starting at 9 months in APP/PS1 mice. Other enzymes of the OXPHOS do not show any alterations. Since amyloid-β (Aβ) plaques are already present from 4 months of age, mitochondrial dysfunction likely occurs downstream of Aβ pathology in this mouse model.

Keywords: Alzheimer’s disease, amyloid beta-peptides, electron transport complex II, electron transport complex IV, mice, mitochondria

DOI: 10.3233/JAD-180337

Journal: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 75-82, 2018