What this means
Whether APOE e4 modifies relationships between subclinical cardiac phenotypes and brain structure is unknown. In Framingham Heart Study Offspring participants, we related antecedent echocardiographic remodeling (Examinations 4-6) to repeated brain MRI, and cardiac magnetic resonance phenotypes to regional cortical morphometry, testing cardiac x APOE e4 interactions with false-discovery-rate (FDR) correction and permutation testing of the regional screen.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Not stated
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- APOE ε4 Modifies the Association of Left Atrial Remodeling With Brain Aging
- Authors
- Badea, A., Xu, J., Laskowitz, D. T. et al.
- Journal
- medRxiv (preprint, not yet peer reviewed)
- Published
- Oct 20, 2026
- Study type
- Preprint
Abstract
Background
Whether APOE e4 modifies relationships between subclinical cardiac phenotypes and brain structure is unknown.
What they did
In Framingham Heart Study Offspring participants, we related antecedent echocardiographic remodeling (Examinations 4-6) to repeated brain MRI, and cardiac magnetic resonance phenotypes to regional cortical morphometry, testing cardiac x APOE e4 interactions with false-discovery-rate (FDR) correction and permutation testing of the regional screen.
What they found
APOE e4 modified the association between antecedent left atrial (LA) remodeling and subsequent lateral ventricular expansion (beta=-0.00858, P=1.45 x 10^-4, q=0.0023; N=1,305; 3,787 MRI observations), the only FDR-significant result of 16 longitudinal tests, including with participant-specific MRI-time slopes (q=0.034); it weakened when intracranial volume x MRI time was modeled. Four regional ventricular cardiac x APOE e4 interactions met within-family FDR criteria, but their number was consistent with chance (permutation P=0.70). Maximum LA volume index showed an APOE e4-dependent association with left middle-occipital cortical-thickness variability (whole-brain q=0.017; permutation P=0.041) that persisted after ventricular adjustment. Cardiac phenotypes and trajectories showed no FDR-significant APOE e4-dependent associations with plasma Abeta42/40, p-tau181, GFAP, or NfL, and adjustment for these biomarkers changed the regional interactions by at most 3.2%. Allen Human Brain Atlas data showed cholesterol-biosynthesis enrichment in the right superior frontal cortex, implicated by the LV end-systolic volume interaction, but without convergent pathway evidence. APOE e4 modified atrial-brain relationships, with the strongest evidence linking antecedent atrial remodeling to later ventricular expansion. Replication with prespecified models is needed.
The authors' abstract, grouped under plain headings from its own section labels.
Badea, A., Xu, J., Laskowitz, D. T. et al. APOE ε4 Modifies the Association of Left Atrial Remodeling With Brain Aging. medRxiv. 2026. doi:10.64898/2026.10.14.26365550. https://doi.org/10.64898/2026.10.14.26365550