生物标志物 生物标志物
Pratishtha Chatterjee1,2,3, Pawel Kalinowski4, Anne M Roberts5
1The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
低脑脊液粉样蛋白前体蛋白 (APP) 水平与阿尔茨海默病 (AD) 痴呆症有关,特别是在具有酸化 (p-tau) 病理的人群中. 这一发现有助于理解非典型的AD生物标志物概况.
科学领域:
- 神经科学是一个神经科学.
- 生物标志物 生物标志物
- 阿尔茨海默病病理生理病理学
背景情况:
- 生物标志物 (粉样β和酸化) 的整合改善了阿尔茨海默病 (AD) 的诊断.
- 非典型的生物标志物概况 (例如,粉样β阳性/酸化阳性) 在临床诊断的阿尔茨海默病例中的15-20%发生,这给诊断带来了挑战.
- 在这些非典型病例中,研究AD类症状的替代病理生理机制至关重要.
研究的目的:
- 为了研究大脑脊髓液 (CSF) 粉样蛋白前体蛋白 (APP) 在临床诊断的AD患者中的作用.
- 探索CSF APP水平与不同生物标志物概况 (粉样β和酸化状态) 之间的关系.
- 了解APP干扰对AD进展和认知衰退的贡献.
主要方法:
- 在两个独立的队列中分析CSF APP度:ADNI (N=384) 和ADC (N=419).
- 对APP含量与酸化陶 (p-tau181) 和Aβ42/Aβ40比率的相关性分析.
- 评估APP水平与其他生物标志物 (NfL) 和认知/功能评分 (MMSE,CDR-SB) 之间的关联.
主要成果:
- 在所有诊断组中,与酸化阳性 (T+) 个体相比,酸化阳性 (T-) 个体的CSF APP显著较低.
- 在临床AD诊断的T-病例中,APP减少最为明显.
- 较低的APP水平,特别是与升高的p-tau181相结合时,与阿尔茨海默氏症类痴呆症的最高患病率以及最严重的认知和功能障碍有关.
结论:
- 低APP水平或高的p-tau181与AD类痴呆症的高患病率有关,当两种标志物都存在时,观察到的最大风险.
- 这些发现揭示了临床诊断的AD中T-状态的独特生物学特征,突出了诊断改进的潜力.
- 在APP的生产和处理中出现的障碍可能会导致AD的进展,影响神经元可塑性和认知功能.
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