Apr 5, 2011

Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage

Human Molecular Genetics
Maria ManczakP Hemachandra Reddy

Abstract

The purpose of our study was to better understand the relationship between mitochondrial structural proteins, particularly dynamin-related protein 1 (Drp1) and amyloid beta (Aβ) in the progression of Alzheimer's disease (AD). Using qRT-PCR and immunoblotting analyses, we measured mRNA and protein levels of mitochondrial structural genes in the frontal cortex of patients with early, definite and severe AD and in control subjects. We also characterized monomeric and oligomeric forms of Aβ in these patients. Using immunoprecipitation/immunoblotting analysis, we investigated the interaction between Aβ and Drp1. Using immunofluorescence analysis, we determined the localization of Drp1 and intraneuronal and oligomeric Aβ in the AD brains and primary hippocampal neurons from Aβ precursor protein (AβPP) transgenic mice. We found increased expression of the mitochondrial fission genes Drp1 and Fis1 (fission 1) and decreased expression of the mitochondrial fusion genes Mfn1 (mitofusin 1), Mfn2 (mitofusin 2), Opa1 (optic atrophy 1) and Tomm40. The matrix gene CypD was up-regulated in AD patients. Results from our qRT-PCR and immunoblotting analyses suggest that abnormal mitochondrial dynamics increase as AD progresses. Immunofluorescence ...Continue Reading

  • References51
  • Citations154

Mentioned in this Paper

Establishment and Maintenance of Localization
DENR gene
Familial Alzheimer Disease (FAD)
Immunofluorescence Assay
MED12 gene
MFN1 gene
Mitochondrial Dynamics
Abnormal Degeneration
APP protein, human
Microtubule-Associated Protein 3

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