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

Yi Guan; Chia Hsin Cheng; Luis I Bellomo; Sriman Narain; Sherman J Bigornia; Mahdi O Garelnabi; Tammy Scott; José M Ordovás; Katherine L Tucker; Rafeeque Bhadelia; Bang-Bon Koo

doi:10.3389/fnagi.2023.1285333

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

Front Aging Neurosci. 2023 Nov 15:15:1285333. doi: 10.3389/fnagi.2023.1285333. eCollection 2023.

Authors

Yi Guan^#¹, Chia Hsin Cheng^#¹, Luis I Bellomo¹, Sriman Narain¹, Sherman J Bigornia², Mahdi O Garelnabi³, Tammy Scott⁴, José M Ordovás^{5

6

7}, Katherine L Tucker^{8

9}, Rafeeque Bhadelia¹⁰, Bang-Bon Koo¹

Affiliations

¹ Department of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United States.
² Department of Agriculture, Nutrition, and Food Systems, College of Life Sciences and Agriculture, University of New Hampshire, Durham, NH, United States.
³ Department of Public Health, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA, United States.
⁴ School of Medicine, Tufts University, Boston, MA, United States.
⁵ Nutrition and Genomics Laboratory, J.M.-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States.
⁶ IMDEA Alimentacion, Madrid, Spain.
⁷ CIBER Fisiopatologia de la Obesidad y la Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
⁸ Department of Biomedical and Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA, United States.
⁹ Center for Population Health, University of Massachusetts Lowell, Lowell, MA, United States.
¹⁰ Neuroradiology Section, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

^# Contributed equally.

Abstract

Background: Apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD), and the ε4 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 state 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.

Conclusion: 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.

Keywords: APOE; aging; blood biomarker; blood–brain barrier; cognitive decline; diet; neurite orientation dispersion and density imaging; neuroinflammation.

Abstract

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