与MAPT相关的前叶退化症的症状前和早期病理特征
Lucia Aa Giannini1, Merel O Mol1, Ana Rajicic1
1Department of Neurology and Alzheimer Center Erasmus MC, Erasmus University Medical Center, Rotterdam, 3015 GD, The Netherlands.
Acta neuropathologica communications
|August 2, 2023
概括
早期的病理和神经元退化存在于带有MAPT变异的前叶退化 (FTLD-MAPT),甚至在症状出现之前. 这些早期的变化,虽然不如后期的阶段那么严重,但显示出变异特异性的模式.
科学领域:
- 神经科学是一个神经科学.
- 神经病理学神经病理学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 带有MAPT变异的前叶退化 (FTLD-MAPT) 是一种神经退行性疾病.
- 由于早期阶段组织的可用性有限,对FTLD-MAPT的早期病理变化知之甚少.
- 已知MAPT基因变异是FTLD的已知原因之一.
研究的目的:
- 调查FTLD-MAPT的早期病理特征.
- 为了比较FTLD-MAPT的预症状/早期病理与中期/末期病理.
- 为特定的MAPT变体开发临床病理阶段模型.
主要方法:
- 从前症状/早期阶段和中期/末期FTLD-MAPT病例中检查了神经元退化和量化了灰色和白质区域的tau负担.
- 在不同的MAPT变体 (L315R,P301L,G272V) 中比较了病理发现.
- 开发了P301L和G272V变体的临床病理阶段模型.
主要成果:
- 在症状前/早期的FTLD-MAPT中存在tau负担和神经元退行,但不如后期的阶段那么严重.
- 在早期阶段,MAPT变体之间的区域tau负担分布在MAPT变体之间存在差异.
- 临床严重程度与神经元退化和灰质tau负担相关,但不是白质tau负担.
- 临床病理学阶段测定揭示了早期tau病理和进展的变异特异性模式.
结论:
- 病理和神经元退化始于FTLD-MAPT的症状前/早期阶段.
- 早期的病理模式,特别是tau负担,在不同的MAPT变体中表现出变化.
- 临床病理学分期模型可以捕捉FTLD-MAPT中的变异特异性疾病进展.
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