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Basic Science and Pathogenesis.

Mariana Chauvet1, Danielle Cozachenco Ferreira2, Alinny Isaac2

  • 1Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

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Summary
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Alzheimer's disease (AD) involves impaired brain mRNA translation. This study found increased levels of phosphorylated eukaryotic initiation factor 2 alpha (eIF2a) and eukaryotic elongation factor 2 (eEF2) in AD brains, correlating with disease severity.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • Alzheimer's disease (AD) is a major cause of dementia, characterized by impaired brain mRNA translation.
  • Protein synthesis, crucial for cognition, involves initiation and elongation factors like eIF2a and eEF2.
  • Aberrant phosphorylation of these factors can lead to translational repression, implicated in AD pathogenesis.

Purpose of the Study:

  • To investigate the role of phosphorylated eIF2a and eEF2 in Alzheimer's disease.
  • To determine if these translational factors correlate with AD neuropathology.

Main Methods:

  • Western blotting was used to measure phosphorylated and total eIF2a and eEF2.
  • Analysis was performed on postmortem hippocampi and prefrontal cortices from healthy controls and AD patients.
  • Correlation with CERAD amyloid score and Braak stage was assessed.

Main Results:

  • Increased levels of phosphorylated eIF2a and eEF2 were observed in AD brains.
  • Elevated phospho-eIF2a and phospho-eEF2 correlated with higher CERAD amyloid scores in the hippocampus and prefrontal cortex.
  • These phosphorylated factors also increased with higher Braak stages in the prefrontal cortex.

Conclusions:

  • Translational factors eIF2a and eEF2, particularly their phosphorylated forms, are altered in Alzheimer's disease.
  • These alterations correlate with amyloid and tau pathology, suggesting a role in AD progression.
  • Further research is needed to fully understand the precise roles of these factors in dementia.