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Pérez MJ, Ponce DP, Osorio-Fuentealba C, et al. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease. Front Neurosci. 2017;11:553doi: 10.3389/fnins.2017.00553.
Pérez, M. J., Ponce, D. P., Osorio-Fuentealba, C., Behrens, M. I., & Quintanilla, R. A. (2017). Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease. Frontiers in neuroscience, 11553. https://doi.org/10.3389/fnins.2017.00553
Pérez, María J, et al. "Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease." Frontiers in neuroscience vol. 11 (2017): 553. doi: https://doi.org/10.3389/fnins.2017.00553
Pérez MJ, Ponce DP, Osorio-Fuentealba C, Behrens MI, Quintanilla RA. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease. Front Neurosci. 2017 Oct 06;11:553. doi: 10.3389/fnins.2017.00553. eCollection 2017. PMID: 29056898; PMCID: PMC5635042.
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Front Neurosci. 2017 Oct 06;11:553. doi: 10.3389/fnins.2017.00553. eCollection 2017.

Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease.

Frontiers in neuroscience

María J Pérez, Daniela P Ponce, Cesar Osorio-Fuentealba, Maria I Behrens, Rodrigo A Quintanilla

Affiliations

  1. Laboratory of Neurodegenerative Diseases, Universidad Autónoma de Chile, Santiago, Chile.
  2. Centro de Investigación y Estudio del Consumo de Alcohol en Adolescentes, Santiago, Chile.
  3. Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile.
  4. Departamento Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Ñuñoa, Chile.

PMID: 29056898 PMCID: PMC5635042 DOI: 10.3389/fnins.2017.00553

Abstract

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.

Keywords: Alzheimer's disease; OPA1; biomarker; fibroblasts; mitochondria

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