Mediterranean vs. Western diet effects on the primate cerebral cortical pre-synaptic proteome: Relationships with the transcriptome and multi-system phenotypes

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-03-20 DOI:10.1002/alz.70041

Eloise Berson, Brett M. Frye, Chandresh R. Gajera, Geetha Saarunya, Amalia Perna, Thanaphong Phongpreecha, Sayane Shome, Jacob D. Negrey, Nima Aghaeepour, Thomas J. Montine, Suzanne Craft, Thomas C. Register, Carol A. Shively

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引用次数: 0

Abstract

INTRODUCTION

Diet quality mediates aging-related risks of cognitive decline, neurodegeneration, and Alzheimer's disease (AD) through poorly defined mechanisms.

METHODS

The effects of diet on the presynaptic proteome of the temporal cortex were assessed in 36 female cynomolgus macaques randomized to Mediterranean or Western diets for 31 months. Associations between the presynaptic proteome, determined by synaptometry by time-of-flight (SynTOF) mass spectrometry, adjacent cortex transcriptome, and multi-system phenotypes were assessed using a machine learning approach.

RESULTS

Six presynaptic proteins (DAT, Aβ42, calreticulin, LC3B, K48-Ubiquitin, SLC6A8) were elevated in the presynaptic proteome in Mediterranean diet consumers (p < 0.05). Transcriptomic data and multi-system phenotypes significantly predicted SynTOF markers. Selected SynTOF markers were correlated with changes in white matter volumes, hepatosteatosis, and behavioral and physiological measures of psychosocial stress.

DISCUSSION

These observations demonstrate that diet composition drives cortical presynaptic protein composition, that transcriptional profiles strongly predict the presynaptic proteomic profile, and that presynaptic proteins were closely associated with peripheral metabolism, stress responsivity, neuroanatomy, and socio-emotional behavior.

Highlights

Mediterranean and Western diets differentially altered the cortical presynaptic proteome, which is strongly associated with neurodegeneration and cognitive decline.
Presynaptic proteomic markers were predicted by transcriptomic profiles in the adjacent cortex, and by multi-system anatomical, physiologic, and behavioral phenotypes.
The data demonstrate that brain phenotypes and brain-body interactions are influenced by common dietary patterns, suggesting that improving diet quality may be an effective means to maintain brain health.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.