Association of dietary fatty acids with longitudinal change in plasma-based biomarkers of Alzheimer's disease - 19/03/25

Doi : 10.1016/j.tjpad.2025.100117

Serena S. Hoost ^c, Lawrence S. Honig ^a,^b,^c, Min Suk Kang ^a,^c, Aanya Bahl ^a, Annie J. Lee ^a,^c, Danurys Sanchez ^a,^c, Dolly Reyes-Dumeyer ^a,^c, Rafael A. Lantigua ^a,^e, Jeffrey L. Dage ^f, Adam M. Brickman ^a,^b,^c, Jennifer J. Manly ^a,^b,^c, Richard Mayeux ^a,^b,^c,^d,^{^{1
The authors contributed equally to this work.}}, Yian Gu ^a,^b,^c,^d,^⁎,^{^{1
The authors contributed equally to this work.}}
^a Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA
^b G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York, 10032, USA
^c Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, 710 West 168th Street, New York, New York, 10032, USA
^d Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, New York, 10032, USA
^e Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, and the New York Presbyterian Hospital, 630 West 168th Street, New York, New York, 10032, USA
^f Stark Neurosciences Research Institute, Suite 414, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, Indiana, 46202, USA

^⁎Corresponding author at: Columbia University Irving Medical Center, 622 W 168th St., pH 18th floor, New York, NY, 10032.Columbia University Irving Medical Center622 W 168th St., pH 18th floorNew YorkNY10032

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Abstract

Background

Elevated intake of omega-3 polyunsaturated fatty acids is linked to a reduced risk of dementia in some prospective studies. However, few studies have examined the relationship between nutrient intake and plasma biomarkers of Alzheimer's disease.

Objectives

We explored whether omega-3, omega-6, and monounsaturated fat intakes were associated with changes in plasma biomarkers of Alzheimer's disease over time.

Design

The Washington Heights-Inwood Columbia Aging Project is a prospective cohort study (1994–2021); the data set used here includes a mean follow-up of 7.0 years.

Setting

Community-based in New York City.

Participants

599 dementia-free individuals at baseline who completed a 61-item food frequency questionnaire and had biomarkers measured in plasma from at least two different time points.

Measurements

Fatty acid intake tertiles were computed from participant-completed 61-item Willett semi-quantitative food frequency questionnaires (Channing Laboratory, Cambridge, Massachusetts) obtained once at their baseline visit. Plasma-based biomarker assays were performed, using the single molecule array technology Quanterix Simoa HD-X platform, at baseline and follow-up visits. Generalized Estimating Equations (GEE) models were used to evaluate the association between baseline nutrient intake tertile and changes in biomarkers including phospho-tau181, amyloid-beta 42/40 ratio, phospho-tau181/amyloid-beta42 ratio, glial fibrillary acidic protein, neurofilament light chain, and two biomarker patterns derived from Principal Component Analysis (PCA1 and PCA2), with higher scores indicating a high level of neurodegeneration and low level of Alzheimer's disease burden, respectively). Models were adjusted for age, sex, race/ethnicity, education, and calculated total energy intake initially, and additionally for cerebrovascular risk factors.

Results

Higher baseline omega-3 intake tertile was associated with lesser decline in PCA2 (β = 0.221, p < 0.001) and amyloid-beta 42/40 ratio (β = 0.022, p = 0.003), and a lesser rise in phospho-tau181 (β = -0.037, p = 0.001). Higher omega-6 intake tertile was linked to a lesser rise in phospho-tau181 (β = -0.050, p < 0.001) and glial fibrillary acidic protein (β = -0.028, p = 0.002). Most associations persisted after adjusting for cardiovascular risk factors.

Conclusions

Higher relative baseline intake of omega-3 and omega-6 fatty acids is associated with lesser progression of blood-based biomarkers of Alzheimer's disease. Consuming healthy fatty acids may help prevent accumulation of Alzheimer's disease-related pathological changes.

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Key Words : Blood-based biomarker, Diet, Omega-3, Alzheimer's disease, Amyloid