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Differential effects of the ApoE4 genotype on brain structure and function.

Silke Matura1, David Prvulovic1, Alina Jurcoane2

  • 1Laboratory of Neurophysiology and Neuroimaging, Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe Univ., Frankfurt/Main, Germany.

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Summary

The apolipoprotein E ε4 allele impacts brain function in young adults, showing altered episodic memory network activity. These functional changes may precede structural neurodegeneration in Alzheimer's disease risk.

Keywords:
Apolipoprotein4DTIMemoryVBMfMRI

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Area of Science:

  • Neuroscience
  • Genetics
  • Alzheimer's Disease Research

Background:

  • The apolipoprotein E ε4 (ApoE ε4) allele is a significant genetic risk factor for sporadic Alzheimer's disease.
  • ApoE ε4 is linked to brain structural and functional changes across various age groups.
  • Early detection of Alzheimer's disease risk markers is crucial for potential interventions.

Purpose of the Study:

  • To investigate the effects of the ApoE genotype on brain structure, cognition, and neural activity in healthy young adults.
  • To determine if ApoE ε4 carriers exhibit differences in brain macrostructure, microstructure, cognitive performance, or episodic memory network activity compared to non-carriers.
  • To explore potential early functional alterations associated with the ApoE ε4 allele.

Main Methods:

  • Utilized diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) for brain macro- and microstructural analysis.
  • Employed a comprehensive neuropsychological battery to assess cognitive functions, particularly episodic memory.
  • Applied event-related functional magnetic resonance imaging (fMRI) to measure brain activity during episodic memory encoding and retrieval tasks.

Main Results:

  • ApoE ε4 carriers demonstrated significant differences in fMRI brain activations during episodic memory tasks compared to non-carriers.
  • No significant differences were observed in cognitive performance or in brain macro- and microstructure between ApoE ε4 carriers and non-carriers.
  • Functional alterations within the episodic memory network were evident in ε4 carriers, independent of structural changes or cognitive deficits.

Conclusions:

  • The presence of the ApoE ε4 allele is associated with functional modifications in the episodic memory network in healthy young adults.
  • These observed functional changes may represent an early biomarker of Alzheimer's disease risk, potentially preceding detectable structural neurodegeneration.
  • The findings highlight the role of the ApoE genotype in modulating brain function related to memory, even in the absence of clinical or structural abnormalities.