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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 9302761, 14 pages
https://doi.org/10.1155/2017/9302761
Research Article

Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer’s Disease

1Centro de Biología Molecular “Severo Ochoa” (UAM-CSIC), Nicolás Cabrera, 1. Cantoblanco 28049 Madrid, Spain
2Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Valderrebollo, 5, 28031 Madrid, Spain
3Brain and Mind Research Institute, Weill Cornell Medical College, Cornell University, 407 E 61st St. 1300 York Avenue, New York, NY 10065, USA
4University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-0667, USA
5Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, UAM, Arzobispo Morcillo, 4, 28029 Madrid, Spain

Correspondence should be addressed to Jesús Avila; se.cisc.mbc@alivaj and Vega García-Escudero; se.mau@oreducse-aicrag.v

Received 31 March 2017; Revised 25 July 2017; Accepted 17 August 2017; Published 19 October 2017

Academic Editor: Icksoo Lee

Copyright © 2017 Patricia Martín-Maestro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sporadic Alzheimer’s disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer’s pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer’s patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer’s disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients’ fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer’s fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging.