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

• Published in: Frontiers in neuroscience Vol. 11; p. 553
• Main Authors: Pérez, María J, Ponce, Daniela P, Osorio-Fuentealba, Cesar, Behrens, Maria I, Quintanilla, Rodrigo A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 06-10-2017; Frontiers Media S.A
• Subjects: Alzheimer's disease; Bioenergetics; biomarker; Biomarkers; Brain; Cell differentiation; Dementia; Experiments; Fibroblasts; Membranes; Metabolism; Mitochondria; Morphology; Neurodegeneration; Neurodegenerative diseases; Neuroscience; OPA1; Parkinson's disease; Pathogenesis; Patients; Proteins; Proteolysis; Chile; United States > US; fibroblasts; OPA1; biomarker; Alzheimer's disease; mitochondria
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2017.00553

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.