APOE ε4 carriage is associated with olfactory-hippocampal tract functional connectivity.
Overview
- Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi,PO Box 1848, University, MS 38677 USA
- School of Nursing and Health Studies, University of Miami,Coral Gables, FL 33124 USA
Abstract
Olfactory dysfunction often emerges before cognitive symptoms and may signal early vulnerability to neurodegenerative processes. This study examined whether genetic risk, specifically the presence of the epsilon 4 allele in apolipoprotein E, is associated with altered functional connectivity between the hippocampus and olfactory regions. Resting-state functional imaging data from 126 participants (mean age = 71.8 years, SD = 6.9; 67 females) across a range of clinical stages were analyzed. Functional connectivity was computed between the hippocampus and four olfactory-related regions: anterior piriform cortex, posterior piriform cortex, olfactory bulb, and olfactory tract. Multiple regression models assessed whether genetic risk, age, sex, and clinical diagnosis predicted connectivity strength. Genetic risk was significantly associated with increased connectivity between the hippocampus and the olfactory tract (model R² = 0.12). A nominal APOE ε4 effect was also observed in the olfactory bulb, although the overall model did not reach significance, while no significant effects were observed in the piriform cortex regions. Clinical diagnosis was not a significant predictor of connectivity in any region. These results suggest that genetic risk is linked to early functional reorganization in specific olfactory-hippocampal pathways, particularly the olfactory tract, independent of clinical progression. The olfactory-hippocampal network may serve as a sensitive target for detecting early brain changes associated with neurodegenerative risk.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
No file of the authors' code could be read here: it is described below, and read at its source.
olemiss.edu/projects/dnl
Availability: 1 check, the latest on 30 September 2026: the link is dead (HTTP 404)
- 30 September 2026: the link is dead (HTTP 404)
Code availability
The functional connectivity codes will be available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 4 keywords, 15 MeSH terms, 1 funder, 50 references.
Cite
This paper
Ikuta, T., Bither, T., & The Alzheimer’s Disease Neuroimaging Initiative. (2026). APOE ε4 carriage is associated with olfactory-hippocampal tract functional connectivity. Brain imaging and behavior, 20(2), 46. https://
BibTeX
@article{ikuta2026apoe,
author = {Ikuta, Toshikazu and Bither, Taylor and {The Alzheimer’s Disease Neuroimaging Initiative}},
title = {{APOE ε4 carriage is associated with olfactory-hippocampal tract functional connectivity}},
journal = {Brain imaging and behavior},
year = {2026},
month = mar,
volume = {20},
number = {2},
pages = {46},
publisher = {Springer Science+Business Media},
issn = {1931-7557},
doi = {10.1007/
url = {https://
pmid = {41820696},
pmcid = {PMC12982280}
}
RIS
TY - JOUR
AU - Ikuta, Toshikazu
AU - Bither, Taylor
AU - The Alzheimer’s Disease Neuroimaging Initiative
TI - APOE ε4 carriage is associated with olfactory-hippocampal tract functional connectivity
T2 - Brain imaging and behavior
J2 - Brain Imaging Behav
PY - 2026
DA - 2026/
VL - 20
IS - 2
SP - 46
SN - 1931-7557
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
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"literal": "The Alzheimer’s Disease Neuroimaging Initiative"
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"container-title-short":
"volume": "20",
"issue": "2",
"page": "46",
"DOI": "10.1007/
"PMID": "41820696",
"PMCID": "PMC12982280",
"ISSN": "1931-7557",
"publisher": "Springer Science+Business Media",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
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2026,
3,
13
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}
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