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The dying of the light: mitochondrial failure in Alzheimer's disease

Kisha J Young-Collier1, Michael McArdle, James P Bennett

  • 1Neuroscience Graduate Program and Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, VA, USA.

Journal of Alzheimer'S Disease : JAD
|November 8, 2011
PubMed

Insights

Brain energy production declines in Alzheimer's disease (AD), marked by reduced mitochondrial mass and impaired respiration. Correcting mitochondrial biogenesis and boosting antioxidant defenses may help slow AD progression.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Reduced cortical glucose metabolism (2-FDG PET) is a biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD).
  • Progression to AD involves further decline in glucose uptake, suggesting worsening brain energy production.

Purpose of the Study:

  • To investigate mitochondrial function, mass, and related gene expression in postmortem frontal cortex of AD patients and controls.
  • To determine the relationship between these mitochondrial changes and amyloid-beta levels in AD.

Main Methods:

  • Analysis of mitochondrial respiration in brain mitochondria.
  • Quantification of respiratory protein levels.
  • Measurement of gene expression for mitochondrial DNA (mtDNA), biogenesis, and antioxidant signaling.

Main Results:

  • Mitochondrial respiration was significantly reduced in AD brains due to a loss of mitochondrial mass.
  • While most respiratory proteins were preserved, gene expression for mtDNA, mitochondrial biogenesis, and antioxidant enzymes was decreased in AD.
  • These mitochondrial alterations were not correlated with amyloid-beta 1-42 peptide levels.

Conclusions:

  • Mitochondrial biogenesis is suppressed in the AD frontal cortex, leading to reduced mitochondrial mass and impaired respiratory capacity.
  • Downregulation of antioxidant proteins exacerbates neuronal dysfunction in AD.
  • Therapeutic strategies for AD may need to address both impaired mitochondrial biogenesis and antioxidant protection.

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