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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
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Apolipoprotein E affects both myelin breakdown and cognition: implications for age-related trajectories of decline

George Bartzokis1, Po H Lu, Daniel H Geschwind

  • 1Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. gbar@ucla.edu

Biological Psychiatry
|July 31, 2007
PubMed
Abstract

Insights

The ApoE4 gene variant accelerates age-related cognitive processing speed decline by promoting myelin breakdown in later-myelinating white matter. This suggests myelin integrity is crucial for maintaining cognitive function in aging individuals.

Area of Science:

  • Neuroscience
  • Gerontology
  • Radiology

Background:

  • Age-related myelin breakdown primarily affects later-myelinating white matter (LMwm) regions.
  • This breakdown may contribute to cognitive processing speed (CPS) decline and increase Alzheimer's disease (AD) risk.
  • The Apolipoprotein E (ApoE) 4 allele is a significant risk factor for AD.

Purpose of the Study:

  • To test if the ApoE4 allele accelerates age-related slowing in CPS via myelin breakdown.
  • To investigate the association between myelin breakdown in LMwm and CPS in healthy older adults.

Main Methods:

  • Magnetic resonance imaging (MRI) was used to measure myelin breakdown (R(2)) in LMwm.
  • Cognitive processing speed (CPS) was assessed in 22 ApoE4+ and 80 ApoE4- individuals.
  • A contrast region and memory task were examined for specificity.

Main Results:

  • A significant association between CPS and LMwm R(2) was found in the ApoE4+ group, independent of age.
  • This association differed significantly between ApoE4+ and ApoE4- groups.
  • No significant associations were found in the contrast region or with the memory task.

Conclusions:

  • A specific link exists between CPS and LMwm myelin breakdown in cognitively normal older adults at higher genetic risk for AD.
  • Findings support the hypothesis that myelin breakdown underlies age-related CPS slowing and that ApoE alleles modify this process.
  • Biomarkers and CPS measures may aid in developing primary prevention strategies for AD.

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