地中海饮食与西方饮食对灵长类动物大脑皮质突触前蛋白质组的影响：与转录组和多系统表型的关系。

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

作者信息

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

机构信息

Department of Pathology, Stanford University, Stanford, California, USA.

Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, California, USA.

出版信息

Alzheimers Dement. 2025 Mar;21(3):e70041. doi: 10.1002/alz.70041.

DOI:10.1002/alz.70041

PMID:40109017

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11923382/

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.

摘要

引言

饮食质量通过尚不明确的机制介导与衰老相关的认知衰退、神经退行性变和阿尔茨海默病（AD）风险。

方法

对36只雌性食蟹猕猴进行研究，将其随机分为两组，分别给予地中海饮食或西方饮食31个月，评估饮食对颞叶皮质突触前蛋白质组的影响。采用机器学习方法评估通过飞行时间突触测量法（SynTOF）质谱测定的突触前蛋白质组、相邻皮质转录组和多系统表型之间的关联。

结果

食用地中海饮食的猕猴，其突触前蛋白质组中有6种突触前蛋白（多巴胺转运体、β淀粉样蛋白42、钙网蛋白、微管相关蛋白1轻链3β、K48泛素、溶质载体家族6成员8）水平升高（p < 0.05）。转录组数据和多系统表型显著预测了SynTOF标记物。选定的SynTOF标记物与白质体积变化、肝脂肪变性以及心理社会应激的行为和生理指标相关。