生物标志物 生物标志物
Larissa Fischer1,2, Jenna N Adams2, Eóin N Molloy1,3
1German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
中间叶 (MTL) 和中后皮层 (PMC) 的功能连接性 (FC) 变化与阿尔茨海默病的病理和记忆力下降有关,特别是在APOE4载体中. 网络变化在休息状态和任务状态之间有所不同.
科学领域:
- 神经科学是一个神经科学.
- 认知科学 认知科学
- 医疗成像医学成像
背景情况:
- 中间叶 (MTL) 和中后皮层 (PMC) 对情节性记忆至关重要,是阿尔茨海默病 (AD) 病理学的早期部位.
- APOE4基因型是阿尔茨海默病的重要风险因素,影响病理积累和认知衰退.
- 在MTL和PMC内部和之间的功能连接 (FC) 变化可能反映了AD病原体中神经网络的补偿性或有害变化.
研究的目的:
- 研究在MTL和PMC和阿尔茨海默氏病理负担内和之间功能连接 (FC) 的纵向变化之间的关系.
- 检查这些FC变化如何与认知表现有关,特别是延迟的记忆回忆和对象识别.
- 探索APOE基因型在这些关联中的调节作用.
主要方法:
- 从PREVENT-AD队列中分析了纵向的3-特斯拉fMRI数据和横截面的粉样β和蛋白PET成像.
- 在对象位置编码过程中静止状态FC (RSFC) 和基于任务的FC的变化在这些区域内 (ΔFCPMC, ΔFCMTL) 和之间 (ΔFCMTL-PMC) 进行了评估.
- 多重回归和线性混合模型被用来研究 ΔFC,病理,记忆变化和 APOE 基因型之间的关联,在 152 名认知不受损的老年人中.
主要成果:
- APOE基因型调节了FC变化和病理之间的关联:降低RSFCPMC与APOE4载体中较高的粉样蛋白相关,而增加编码-FCMTL与APOE4载体中较高的tau相关.
- 不管APOE状态如何,加密-FCPMC的增加与较差的内存性能 (RBANS和对象识别) 有关.
- 增加的RSFCMTL-PMC与改善的RBANS性能有关,而增加的编码-FCMTL-PMC与物体识别的降低有关.
结论:
- 在MTL和PMC内部和之间的纵向FC变化显示了与AD病理学和记忆表现的APOE-依赖性关联.
- 网络变化在休息条件和任务条件中表现得不同,这凸显了动态FC评估的重要性.
- 在APOE4载体中,编码期间增加的MTL连接与tau病理有关,而休息期间减少的PMC连接与粉样蛋白有关,这表明这些区域存在不同的病理机制.
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