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. 2024 Jul 5;16(3):e12596.
doi: 10.1002/dad2.12596. eCollection 2024 Jul-Sep.

Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer's disease dementia

Iolanda Lázaro  1   2   3 , Oriol Grau-Rivera  1   2   4   5 , Marc Suárez-Calvet  1   2   4   5 , Karine Fauria  2   4 , Carolina Minguillón  1   2   4 , Mahnaz Shekari  1   2   4   6 , Carles Falcón  2   7 , Marina García-Prat  2 , Jordi Huguet  2 , José Luis Molinuevo  2   8 , Juan-Domingo Gispert  1   2   7 , Aleix Sala-Vila  1   2   3   9 ; ALFA study
Affiliations

Omega-3 blood biomarkers relate to brain glucose uptake in individuals at risk of Alzheimer's disease dementia

Iolanda Lázaro et al. Alzheimers Dement (Amst). .

Abstract

Introduction: Brain glucose hypometabolism is a preclinical feature of Alzheimer's disease (AD). Dietary omega-3 fatty acids promote brain glucose metabolism, but clinical research is incipient. Circulating omega-3s objectively reflect their dietary intake.

Methods: This was a cross-sectional study in 320 cognitively unimpaired participants at increased risk of AD dementia. Using lipidomics, we determined blood docosahexaenoic (DHA) and alpha-linolenic (ALA) acid levels (omega-3s from marine and plant origin, respectively). We assessed brain glucose metabolism using [18-F]-fluorodeoxyglucose (FDG) positron emission tomography (PET).

Results: Blood ALA directly related to FDG uptake in brain areas known to be affected in AD. Stronger associations were observed in apolipoprotein E ε4 carriers and homozygotes. For DHA, significant direct associations were restricted to amyloid beta-positive tau-positive participants.

Discussion: Blood omega-3 directly relate to preserved glucose metabolism in AD-vulnerable brain regions in individuals at increased risk of AD dementia. This adds to the benefits of omega-3 supplementation in the preclinical stage of AD dementia.

Highlights: Blood omega-3s were related to brain glucose uptake in participants at risk of Alzheimer's disease (AD) dementia.Complementary associations were observed for omega-3 from marine and plant sources.Foods rich in omega-3 might be useful in early features of AD.

Keywords: biomarkers; diet; fatty fish; fish oil; nuts; n‐3 fatty acids; polyunsaturated fatty acids; walnuts.

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Conflict of interest statement

MSC has given lectures in symposia sponsored by Roche Diagnostics, S.L.U. Roche Farma, S.A., and Amirall;and he has served as a consultant and at advisory boards for Roche Diagnostics International Ltd and Grifols S.L. He was granted with a project funded by Roche Diagnostics International Ltd; payments were made to the institution (BBRC). He received in‐kind support for research (to the institution) from Roche Diagnostics International Ltd, Avid Radiopharmaceuticals, Inc., Eli Lilly, and Janssen Research & Development. JLM is currently a full‑time employee of H. Lundbeck A/S and previously served as a consultant or on advisory boards for the following for‑profit companies or has given lectures in symposia sponsored by the following for‑profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, and ProMIS Neurosciences. JDG receives research funding from Roche Diagnostics and GE Healthcare and has given lectures at symposia sponsored by Biogen and Philips. AS‐V has received research grant funding through his institution and support to attend professional meetings from the California Walnut Commission. Other authors report no conflicts of interest. Disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Association of DHA with [18‐F]‐FDG uptake by AT status. Scatterplots of the association between RBC DHA and standardized residuals of FDG uptake (SUVR), outputted from a general linear model including age, sex, years of education, days between blood sampling and [18‐F]‐FDG PET acquisition, and APOE ε4 carriership (A), and further inclusion of BMI, ever smoking, hypertension, dyslipidemia, and diabetes (B). Each point depicts the value of an individual, and the solid lines indicate the regression line for each of the groups. Data include Pearson correlation coefficients and P values for each subgroup of interest. APOE, apolipoprotein E; AT, amyloid/tau; BMI, body mass index; DHA, docosahexaenoic acid; FDG, fluorodeoxyglucose; PET, positron emission tomography; RBC, red blood cell; SUVR, standardized uptake value ratio.
FIGURE 2
FIGURE 2
Association of ALA with [18‐F]‐FDG uptake by APOE ε4 status. Scatterplots of the association between RBC ALA and standardized residuals of FDG uptake (SUVR), outputted from a general linear model including age, sex, years of education, and days between blood sampling and [18‐F]‐FDG PET acquisition (A, C, and E), and further inclusion of BMI, ever smoking, hypertension, dyslipidemia, and diabetes (B, D, and F). Each point depicts the value of an individual, and the solid lines indicate the regression line for each of the groups. Data include Pearson correlation coefficients and P values for each subgroup of interest. ALA, alpha‐linolenic acid; APOE, apolipoprotein E; BMI, body mass index; FDG, fluorodeoxyglucose; PET, positron emission tomography; RBC, red blood cell; SUVR, standardized uptake value ratio.
FIGURE 3
FIGURE 3
Three‐dimensional brain statistical parametric maps highlighting in red areas the positive associations between red blood cell ALA and preserved [18‐F]‐FDG uptake.
See this image and copyright information in PMC

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