Wesenhagen Kirsten E J, de Leeuw Diederick M, Tomassen Jori, Gobom Johan, Bos Isabelle, Vos Stephanie J B, Martinez-Lage Pablo, Tainta Mikel, Popp Julius, Peyratout Gwendoline, Tsolaki Magda, Vandenberghe Rik, Freund-Levi Yvonne, Verhey Frans, Lovestone Simon, Streffer Johannes, Dobricic Valerija, Blennow Kaj, Scheltens Philip, Smit August B, Bertram Lars, Teunissen Charlotte E, Zetterberg Henrik, Tijms Betty M, Visser Pieter Jelle
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, the Netherlands.
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden.
Alzheimers Res Ther. 2025 Mar 3;17(1):56. doi: 10.1186/s13195-025-01703-z.
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.
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.
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.
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.
我们研究了正常认知（CN）和轻度认知障碍（MCI）患者脑脊液中突触蛋白水平与记忆功能之间的关系，并研究了淀粉样蛋白阳性对这些关系的影响。
我们纳入了来自欧洲阿尔茨海默病多模态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）的242名CN患者（105名（43%）淀粉样蛋白异常）和278名MCI患者（183名（66%）淀粉样蛋白异常）。对于SynGO中具有突触注释的181种（EMIF-AD MBD）和36种（ADNI）蛋白质，使用线性模型分析其与单词学习回忆的关系。
在临床前AD（EMIF-AD MBD：7种，ADNI：5种蛋白质，无重叠）、前驱AD（仅EMIF-AD MBD，27种蛋白质）和非AD MCI（EMIF-AD MBD：1种，ADNI：7种蛋白质）中，部分突触蛋白水平越低，回忆越差。这些关联大多特定于这些临床组。
与突触功能障碍相关的记忆损害在AD早期就已出现，这表明在疾病早期开发针对突触的治疗方法可能具有重要意义。
