APOE ε4 Carriage is Associated with Hippocampus-Olfactory Tract Functional Connectivity
Toshikazu Ikuta1, Taylor Bither2
1University of Mississippi.
Research Square
|June 30, 2025
Summary
Genetic risk for neurodegeneration is linked to stronger connections between the hippocampus and olfactory pathways, specifically the olfactory bulb and tract. This suggests early brain changes detectable before clinical symptoms appear.
Area of Science:
- Neuroscience
- Genetics
- Neuroimaging
Background:
- Olfactory dysfunction can precede cognitive decline in neurodegenerative diseases.
- Apolipoprotein E (APOE) epsilon 4 allele is a known genetic risk factor for neurodegeneration.
- Early detection of neurodegenerative vulnerability is crucial.
Purpose of the Study:
- To investigate the association between genetic risk (APOE e4) and functional connectivity in olfactory-hippocampal pathways.
- To determine if genetic risk influences brain connectivity independently of clinical diagnosis.
Main Methods:
- Resting-state functional MRI data from 126 older adults were analyzed.
- Functional connectivity was calculated between the hippocampus and olfactory regions (olfactory bulb, olfactory tract, piriform cortex).
- Multiple regression models examined predictors of connectivity strength, including genetic risk, age, sex, and diagnosis.
Main Results:
- APOE e4 carrier status was significantly associated with increased hippocampal connectivity to the olfactory bulb and olfactory tract.
- No significant association was found between genetic risk and connectivity in the piriform cortex.
- Clinical diagnosis did not predict functional connectivity in any olfactory-hippocampal region.
Conclusions:
- Genetic risk for neurodegeneration is linked to early functional reorganization in olfactory-hippocampal pathways.
- The olfactory tract shows altered connectivity in individuals with genetic risk, irrespective of clinical stage.
- The olfactory-hippocampal network may serve as a sensitive biomarker for early neurodegenerative changes.
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