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液相色谱-串联质谱蛋白质组学鉴定出在9年随访期间与认知相关的血浆蛋白。

LC-MS/MS proteomics identifies plasma proteins related to cognition over 9-year follow-up.

作者信息

Adegboye Hailey A, Patterson Khiry L, Libby Julia, Sun Yunyi, Zhang Panpan, Liu Dandan, Robb W Hudson, Peterson Amalia J, Cole Keith R, Arul Albert B, Oliver Nekesa C, Whitaker Marsalas D, Pechman Kimberly R, Dumitrescu Logan, Bolton Corey J, Blennow Kaj, Zetterberg Henrik, Hohman Timothy J, Robinson Renã A S, Jefferson Angela L

机构信息

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

出版信息

Alzheimers Dement. 2025 Jun;21(6):e70276. doi: 10.1002/alz.70276.

DOI:10.1002/alz.70276
PMID:40469059
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12138273/
Abstract

INTRODUCTION: This project identified plasma proteins predictive of cognitive decline across a robust neuropsychological protocol over a 9-year period. METHODS: Vanderbilt Memory and Aging Project participants (n = 336, 73 ± 7 years, 59% male, 87% non-Hispanic White, 10% Black/African American) underwent blood draw for baseline plasma protein abundance using mass spectrometry analysis of tandem mass tag (TMT)-labeled peptides and serial neuropsychological assessment (follow-up = 6.1 ± 2.3 years). Linear mixed-effects regressions related protein levels to neuropsychological outcomes in fully adjusted models. False discovery rate correction was applied. RESULTS: Initial proteomics analyses yielded 3764 unique protein identifications across 23 16-plex TMT batches, and 686 proteins passed quality control. Proteins were identified predicting longitudinal decline in language (EGFR, RTN4RL2), information processing speed (EGFR, NOMO2, CLEC3B), executive function (A1BG), and visuospatial skills (RTN4RL2, GALNT1, SERPINA4, SERPINA5, C8A, ALDOB), but not episodic memory. DISCUSSION: Large-scale proteomics analyses identified 10 plasma proteins that predicted subsequent cognitive decline over a 9-year follow-up in multiple cognitive domains. HIGHLIGHTS: There were 3764 unique protein identifications across 23 16-plex TMT batches. Rigorous quality control yielded 686 proteins used as predictors in analyses. Identified proteins related to all domains assessed, except for episodic memory. Many proteins identified were differentially expressed in MCI.

摘要

引言：本项目通过一项为期9年的稳健神经心理学方案，确定了可预测认知衰退的血浆蛋白。 方法：范德比尔特记忆与衰老项目的参与者（n = 336，73±7岁，59%为男性，87%为非西班牙裔白人，10%为黑人/非裔美国人）接受采血，通过串联质谱标签（TMT）标记肽段的质谱分析测定基线血浆蛋白丰度，并进行系列神经心理学评估（随访时间 = 6.1±2.3年）。在完全调整模型中，采用线性混合效应回归分析蛋白水平与神经心理学结果之间的关系。应用错误发现率校正。 结果：最初的蛋白质组学分析在23个16重TMT批次中产生了3764种独特的蛋白质鉴定结果，686种蛋白质通过了质量控制。鉴定出的蛋白质可预测语言能力（表皮生长因子受体、RTN4RL2）、信息处理速度（表皮生长因子受体、NOMO2、CLEC3B）、执行功能（载脂蛋白A1）和视觉空间技能（RTN4RL2、GALNT1、丝氨酸蛋白酶抑制剂A4、丝氨酸蛋白酶抑制剂A5、补体C8a、醛缩酶B）的纵向衰退，但不能预测情景记忆。 讨论：大规模蛋白质组学分析确定了10种血浆蛋白，这些蛋白在9年随访期间可预测多个认知领域随后的认知衰退。 要点：在23个16重TMT批次中共有3764种独特的蛋白质鉴定结果。严格的质量控制产生了686种蛋白质用作分析中的预测指标。鉴定出的蛋白质与所有评估领域相关，但情景记忆除外。许多鉴定出的蛋白质在轻度认知障碍中差异表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/e3b31cd7e9d7/ALZ-21-e70276-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/7f8a53ce6111/ALZ-21-e70276-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/28ab28d4f084/ALZ-21-e70276-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/43c259e25bb3/ALZ-21-e70276-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/662c3930896a/ALZ-21-e70276-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/2dfc51ba4200/ALZ-21-e70276-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/9545539e1957/ALZ-21-e70276-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/10506b48590d/ALZ-21-e70276-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/e3b31cd7e9d7/ALZ-21-e70276-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/7f8a53ce6111/ALZ-21-e70276-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/28ab28d4f084/ALZ-21-e70276-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/43c259e25bb3/ALZ-21-e70276-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/662c3930896a/ALZ-21-e70276-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/2dfc51ba4200/ALZ-21-e70276-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/9545539e1957/ALZ-21-e70276-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/10506b48590d/ALZ-21-e70276-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/12138273/e3b31cd7e9d7/ALZ-21-e70276-g002.jpg

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本文引用的文献

[1]
Plasma proteomics identify biomarkers and undulating changes of brain aging.

Nat Aging. 2025-1

[2]
Targeting terminal pathway reduces brain complement activation, amyloid load and synapse loss, and improves cognition in a mouse model of dementia.

Brain Behav Immun. 2024-5

[3]
Subsequent correlated changes in complement component 3 and amyloid beta oligomers in the blood of patients with Alzheimer's disease.

Alzheimers Dement. 2024-4

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Plasma proteomic profiles predict future dementia in healthy adults.

Nat Aging. 2024-2

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Alzheimers Res Ther. 2024-1-18

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The SERPINA5 coding variant E228Q does not contribute to clinicopathologic characteristics in Alzheimer's disease: A cross-sectional study.

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Establishing Quality Control Procedures for Large-Scale Plasma Proteomics Analyses.

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