Synaptic protein CSF levels relate to memory scores in individuals without dementia.

IF 7.9 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's Research & Therapy Pub Date : 2025-03-03 DOI:10.1186/s13195-025-01703-z

Kirsten E J Wesenhagen, Diederick M de Leeuw, Jori Tomassen, Johan Gobom, Isabelle Bos, Stephanie J B Vos, Pablo Martinez-Lage, Mikel Tainta, Julius Popp, Gwendoline Peyratout, Magda Tsolaki, Rik Vandenberghe, Yvonne Freund-Levi, Frans Verhey, Simon Lovestone, Johannes Streffer, Valerija Dobricic, Kaj Blennow, Philip Scheltens, August B Smit, Lars Bertram, Charlotte E Teunissen, Henrik Zetterberg, Betty M Tijms, Pieter Jelle Visser

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引用次数: 0

Abstract

Background: We investigated how cerebrospinal fluid levels of synaptic proteins associate with memory function in normal cognition (CN) and mild cognitive impairment (MCI), and investigated the effect of amyloid positivity on these associations.

Methods: We included 242 CN (105(43%) abnormal amyloid), and 278 MCI individuals (183(66%) abnormal amyloid) from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). For 181 (EMIF-AD MBD) and 36 (ADNI) proteins with a synaptic annotation in SynGO, associations with word learning recall were analysed with linear models.

Results: Subsets of synaptic proteins showed lower levels with worse recall in preclinical AD (EMIF-AD MBD: 7, ADNI: 5 proteins, none overlapping), prodromal AD (EMIF-AD MBD only, 27 proteins) and non-AD MCI (EMIF-AD MBD: 1, ADNI: 7 proteins). The majority of these associations were specific to these clinical groups.

Conclusions: Synaptic disturbance-related memory impairment occurred very early in AD, indicating it may be relevant to develop therapies targeting the synapse early in the disease.

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突触蛋白CSF水平与无痴呆个体的记忆评分有关。

背景：我们研究了正常认知（CN）和轻度认知障碍（MCI）患者脑脊液突触蛋白水平与记忆功能的关系，并研究了淀粉样蛋白阳性对这些关系的影响。方法：我们从欧洲阿尔茨海默病多模式生物标志物发现医学信息框架（EMIF-AD MBD）和阿尔茨海默病神经影像学倡议（ADNI）中纳入242例CN（105例（43%）异常淀粉样蛋白）和278例MCI个体（183例（66%）异常淀粉样蛋白）。对SynGO中有突触注释的181个（EMIF-AD MBD）和36个（ADNI）蛋白，用线性模型分析了它们与单词学习回忆的关系。结果：在临床前AD （EMIF-AD MBD: 7个，ADNI: 5个蛋白，无重叠）、前驱AD （EMIF-AD MBD仅，27个蛋白）和非AD MCI （EMIF-AD MBD: 1个，ADNI: 7个蛋白）中，突触蛋白亚群水平较低，回忆较差。这些关联大多是这些临床组特有的。结论：突触紊乱相关的记忆障碍在阿尔茨海默病中很早就发生了，这表明在疾病早期开发针对突触的治疗方法可能是相关的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.