Plasma protein risk scores for mild cognitive impairment and Alzheimer's disease in the Framingham heart study

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-03-29 DOI:10.1002/alz.70066

Habbiburr Rehman, Ting Fang Alvin Ang, Qiushan Tao, Rhoda Au, Lindsay A. Farrer, Wei Qiao Qiu, Xiaoling Zhang, for the Alzheimer's Disease Neuroimaging Initiative

{"title":"Plasma protein risk scores for mild cognitive impairment and Alzheimer's disease in the Framingham heart study","authors":"Habbiburr Rehman, Ting Fang Alvin Ang, Qiushan Tao, Rhoda Au, Lindsay A. Farrer, Wei Qiao Qiu, Xiaoling Zhang, for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/alz.70066","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>It is unclear whether aggregated plasma protein risk scores (PPRSs) could be useful in predicting the risks of mild cognitive impairment (MCI) and Alzheimer's disease (AD).</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>The Cox proportional hazard model with the Least Absolute Shrinkage and Selection Operator penalty was used to build the PPRSs for MCI and AD in 1515 Framingham Heart Study Generation 2 with 1128 proteins measured in plasma at exam 5 (cognitively normal [CN] = 1258, MCI = 129, AD = 128).</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>MCI PPRS had a hazard ratio (HR) of 6.97 [5.34, 9.12], with a discriminating power (C-index = 82.52%). AD PPRS had a HR of 5.74 [4.67, 7.05] (C-index = 88.15%). Both PPRSs were also significantly associated with cognitive changes, brain atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were involved in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>This study suggests that PPRSs serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD-related pathogenesis in the brain.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>PPRSs were developed for the risk of AD and AD preclinical stage, MCI.</li>\n \n <li>PPRSs were developed for MCI and AD associated with cognitive changes, loss of brain volume, and increasing level of plasma AD biomarkers.</li>\n \n <li>Leukocyte, chemotaxis, immunity, inflammation, and cellular migration enriched in proteins were identified as being involved in MCI and AD PPRSs.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70066","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/alz.70066","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

INTRODUCTION

It is unclear whether aggregated plasma protein risk scores (PPRSs) could be useful in predicting the risks of mild cognitive impairment (MCI) and Alzheimer's disease (AD).

METHODS

The Cox proportional hazard model with the Least Absolute Shrinkage and Selection Operator penalty was used to build the PPRSs for MCI and AD in 1515 Framingham Heart Study Generation 2 with 1128 proteins measured in plasma at exam 5 (cognitively normal [CN] = 1258, MCI = 129, AD = 128).

RESULTS

MCI PPRS had a hazard ratio (HR) of 6.97 [5.34, 9.12], with a discriminating power (C-index = 82.52%). AD PPRS had a HR of 5.74 [4.67, 7.05] (C-index = 88.15%). Both PPRSs were also significantly associated with cognitive changes, brain atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were involved in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration.

DISCUSSION

This study suggests that PPRSs serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD-related pathogenesis in the brain.

Highlights

PPRSs were developed for the risk of AD and AD preclinical stage, MCI.
PPRSs were developed for MCI and AD associated with cognitive changes, loss of brain volume, and increasing level of plasma AD biomarkers.
Leukocyte, chemotaxis, immunity, inflammation, and cellular migration enriched in proteins were identified as being involved in MCI and AD PPRSs.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

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.