在临床前的自体主导性阿尔茨海默氏症中,先进的结构性大脑衰老
Peter R Millar1, Brian A Gordon2, Julie K Wisch3
1Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA. pmillar@wustl.edu.
Molecular neurodegeneration
|December 19, 2023
概括
大脑预测年龄差距 (BAG) 显示在自体主导阿尔茨海默病 (ADAD) 突变携带者中大脑晚年衰老,在症状出现前长达7年. BAG与阿尔茨海默病的生物标志物和认知相关,提供了基于MRI的简单测量.
科学领域:
- 神经成像和计算神经科学
- 神经学和阿尔茨海默病的研究研究.
背景情况:
- 大脑预测年龄使用神经成像数据估计生物年龄.
- 大脑年龄差距 (BAG) 在散发性阿尔茨海默病 (AD) 中升高.
- 自体主导AD (ADAD) 中的BAG尽管有可预测的进展,但仍未得到充分研究.
研究的目的:
- 在患有自体主导阿尔茨海默氏症 (ADAD) 个体中建模大脑年龄差距 (BAG).
- 研究BAG与ADAD突变状态,认知状态和疾病进展的关联.
- 将BAG与已确定的AD生物标志物和神经成像测量方法进行比较.
主要方法:
- 在257个ADAD突变载体和179个非载体中使用结构性MRI模拟BAG.
- 评估了BAG与突变状态,认知状态和估计的症状发作之间的关联.
- 与粉样蛋白PET,脑液/血pTau-181,NfL和认知测试表现相关联的BAG.
主要成果:
- 在ADAD突变携带者中观察到晚期大脑衰老 (BAG) ~在预期症状出现前7年.
- BAG显示与粉样蛋白PET的中度关联,与pTau-181,NfL和认知有很强的关联.
- BAG的变异性受到ADAD突变变体,性别和教育水平的影响.
结论:
- 大脑年龄差距 (BAG) 是ADAD的有效衡量标准,与零星AD的发现一致.
- BAG有效地与AD关键的神经病理标志物 (pTau,神经退行) 和认知衰退相关.
- BAG提供了一个简单,可解释的基于MRI的AD相关的大脑衰老量化,即使与最小的混因素.
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