Apolipoprotein-E deficiency leads to brain network alteration characterized by diffusion MRI and graph theory
Margaret Caroline Stapleton1,2, Stefan Paul Koch3,4,5, Devin Raine Everaldo Cortes1,2,6
1Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Frontiers in Neuroscience
|December 11, 2023
Summary
Apolipoprotein-E (ApoE) influences brain network development, impacting Alzheimer's disease risk. ApoE deficiency alters brain connectivity, potentially affecting cognitive resilience in aging individuals.
Area of Science:
- Neuroscience
- Genetics
- Aging Research
Background:
- Late-onset Alzheimer's disease (LOAD) is a significant concern for the elderly, marked by cognitive decline.
- Apolipoprotein-E (ApoE) is a known genetic risk factor for LOAD, but its precise role remains unclear.
- The neurodevelopmental origins of ApoE's influence on LOAD risk via brain network architecture are hypothesized.
Purpose of the Study:
- To investigate the impact of ApoE on brain network structure and topology.
- To explore how ApoE deficiency affects brain network development and organization.
- To determine if altered brain networks in ApoE-deficient mice correlate with potential LOAD risk modulation.
Main Methods:
- Diffusion tensor imaging (DTI) was used to analyze brain network structure in adult ApoE knockout (ApoE KO) and wild-type (WT) mice.
- Graph theory analysis was applied to delineate brain network topology and connectivity patterns.
- Comparisons of hemispheric connectivity, functional integration, network efficiency, and segregation were made between ApoE KO and WT groups.
Main Results:
- Significant differences in connectivity were observed between hemispheres and specific brain regions (hippocampus, amygdala, caudate putamen) in ApoE KO mice compared to WT.
- ApoE KO mice exhibited decreased functional integration, network efficiency, and network segregation.
- Brain network development differed between ApoE KO and WT mice by 5 months of age, particularly involving the hippocampus, amygdala, and caudate putamen.
Conclusions:
- Apolipoprotein-E plays a crucial role in the developmental trajectory of brain network architecture.
- Altered brain network development in the absence of ApoE may represent a mechanism modulating the risk for late-onset Alzheimer's disease.
- These findings suggest ApoE's involvement in establishing brain network structures that influence cognitive resilience or vulnerability to LOAD.
