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

Serena S Hoost; Lawrence S Honig; Min Suk Kang; Aanya Bahl; Annie J Lee; Danurys Sanchez; Dolly Reyes-Dumeyer; Rafael A Lantigua; Jeffrey L Dage; Adam M Brickman; Jennifer J Manly; Richard Mayeux; Yian Gu

doi:10.1016/j.tjpad.2025.100117

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

J Prev Alzheimers Dis. 2025 May;12(5):100117. doi: 10.1016/j.tjpad.2025.100117. Epub 2025 Mar 18.

Authors

Affiliations

¹ 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.
² 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; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York, 10032, USA; 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.
³ 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; 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.
⁴ 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.
⁵ 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; 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.
⁶ Stark Neurosciences Research Institute, Suite 414, Indiana University School of Medicine, 320 West 15th Street, Indianapolis, Indiana, 46202, USA.
⁷ 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; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York, 10032, USA; 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; Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, New York, 10032, USA.
⁸ 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; G.H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York, 10032, USA; 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; Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, New York, 10032, USA. Electronic address: yg2121@cumc.columbia.edu.

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.

Keywords: Alzheimer's disease; Amyloid; Blood-based biomarker; Diet; Omega-3.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / blood
Amyloid beta-Peptides / blood
Biomarkers / blood
Dietary Fats*
Fatty Acids, Omega-3* / administration & dosage
Fatty Acids, Omega-6 / administration & dosage
Female
Glial Fibrillary Acidic Protein / blood
Humans
Longitudinal Studies
Male
New York City
Prospective Studies
tau Proteins / blood

Substances

Biomarkers
Amyloid beta-Peptides
tau Proteins
Fatty Acids, Omega-3
Dietary Fats
Fatty Acids, Omega-6
Glial Fibrillary Acidic Protein

Abstract

MeSH terms

Substances

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