APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts

Authors: GUAN, YI - Boston University; CHENG, CHIA HSIN - Boston University; BELLOMO, LUIS - Boston University; NARAIN, SRIMAN - Boston University; BIGORNIA, SHERMAN - University Of New Hampshire; GARELNABI, MAHDI - University Of Massachusetts; SCOTT, TAMMY - Tufts University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TUCKER, KATHERINE - University Of Massachusetts; BHADELIA, RAFEEQUE - Harvard Medical School; KOO, BANG-BON - Boston University

Submitted to: Frontiers in Aging Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2023
Publication Date: 11/15/2023
Citation: Guan, Y., Cheng, C., Bellomo, L.I., Narain, S., Bigornia, S., Garelnabi, M., Scott, T., Ordovas, J.M., Tucker, K.L., Bhadelia, R., Koo, B. 2023. APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2023.1285333.
DOI: https://doi.org/10.3389/fnagi.2023.1285333

Interpretive Summary: Boston-based researchers studied older adults of Puerto Rican descent to understand how genetics and lifestyle might affect brain health and the risk of Alzheimer's Disease. They focused on the APOE4 gene, known to increase Alzheimer's risk. The study included 156 participants and compared those with the APOE4 gene to those without it. They looked at their diets, blood tests, brain scans, and memory tests over about 12 years. The findings showed that people with the APOE4 gene had more changes in certain brain areas and scored lower on memory tests compared to those without the gene. These changes were linked to their diets and blood markers, suggesting that what they ate and their blood health could be connected to their brain health. The study highlights that genetics and lifestyle together might influence brain aging and the risk of Alzheimer's, especially for those with the APOE4 gene.

Technical Abstract: Background: Apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD), and the E4 allele (APOE4) may interact with lifestyle factors that relate to brain structural changes, underlying the increased risk of AD. However, the exact role of APOE4 in mediating interactions between the peripheral circulatory system and the central nervous system, and how it may link to brain and cognitive aging requires further elucidation. In this analysis, we investigated the association between APOE4 carrier status and multimodal biomarkers (diet, blood markers, clinical diagnosis, brain structure, and cognition) in the context of gene-environment interactions. Methods: Participants were older adults from a longitudinal observational study, the Boston Puerto Rican Health Study (BPRHS), who self-identified as of Puerto Rican descent. Demographics, APOE genotype, diet, blood, and clinical data were collected at baseline and at approximately 12th year, with the addition of multimodal brain magnetic resonance imaging (MRI) (T1-weighted and diffusion) and cognitive testing acquired at 12-year. Measures were compared between APOE4 carriers and non-carriers, and associations between multimodal variables were examined using correlation and multivariate network analyses within each group. Results: A total of 156 BPRHS participants (mean age at imaging = 68 years, 77% female, mean follow-up 12.7 years) with complete multimodal data were included in the current analysis. APOE4 carriers (n=43) showed reduced medial temporal lobe (MTL) white matter (WM) microstructural integrity and lower mini-mental status examination (MMSE) score than non-carriers (n=113). This pattern was consistent with an independent sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) of n=283 non-Hispanic White adults without dementia (mean age =75, 40% female). Within BPRHS, carriers showed distinct connectivity patterns between multimodal biomarkers, characterized by stronger direct network connections between baseline diet/blood markers with 12-year blood/clinical measures, and between blood markers (especially lipids and cytokines) and WM. Cardiovascular burden (i.e., hypertension and diabetes status) was associated with WM integrity for both carriers and non-carriers.APOE4 carrier status affects interactions between dietary factors, multimodal blood biomarkers, and MTL WM integrity across ~12 years of follow-up, which may reflect increased peripheral-central systems crosstalk following blood-brain barrier breakdown in carriers.