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Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts

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Abstract

Mitochondrial dysfunction is observed in brains of Alzheimer’s Disease patients as well as many rodent model systems including those modeling mutations in preseinilin 1 (PSEN1). The aim of our study was to characterize mitochondrial function and number in fibroblasts from AD patients with PSEN1 mutations. We used biochemical assays, metabolic profiling and fluorescent labeling to assess mitochondrial number and function in fibroblasts from three AD patients compared to fibroblasts from three controls. The mutant AD fibroblasts had increased Aβ42 relative to controls along with reduction in ATP, basal and maximal mitochondrial respiration as well as impaired spare mitochondrial respiratory capacity. Fluorescent staining and expression of genes encoding electron transport chain enzymes showed diminished mitochondrial content in the AD fibroblasts. This study demonstrates that mitochondrial dysfunction is observable in AD fibroblasts and provides evidence that this model system could be useful as a tool to screen disease-modifying compounds.

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Acknowledgments

This work was funded by a Department of Veterans Affairs Merit Review grant awarded to J. Quinn.

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Authors and Affiliations

  1. Department of Neurology, Oregon Health and Science University, Portland, OR, 97239, USA

    Nora E. Gray & Joseph F. Quinn

  2. Department of Neurology and Parkinson’s Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, 97239, USA

    Joseph F. Quinn

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  1. Nora E. Gray
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  2. Joseph F. Quinn
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Correspondence to Nora E. Gray.

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Gray, N.E., Quinn, J.F. Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts. Metab Brain Dis 30, 1275–1278 (2015). https://doi.org/10.1007/s11011-015-9667-z

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  • DOI: https://doi.org/10.1007/s11011-015-9667-z

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