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Journal of Alzheimer's Disease





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All authors are part of the VCU Parkinson's & Movement Disorders Center.

Ann C. Rice1,2, Paula M. Keeney1, Norah K. Algarzae1, Amy C. Ladd1, Ravindar R. Thomas1 and James P. Bennett, Jr.1,2,3,4

1Parkinson’s Disease Center, 2Departments of Neurology, 3Psychiatry and 4Physiology and Biophysics Virginia Commonwealth University

Date of Submission

March 2015


Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aβ1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aβ25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD.


© 2014 IOS Press and the authors. This is the author’s version of a work that was accepted for publication in Journal of Alzheimer's Disease, vol. 40 iss. 2 (2014) 319–330. The final publication is available at

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