Humpel Christian
Laboratory of Psychiatry and Experimental Alzheimer's Research, Medical University of Innsbruck, Innsbruck, Austria.
Front Dement. 2025 Jul 25;4:1585124. doi: 10.3389/frdem.2025.1585124. eCollection 2025.
Alzheimer's disease (AD) is a severe neurodegenerative brain disorder molecularly characterized by extracellular β-amyloid plaques, intraneuronal tau neurofibrillary tangles, cholinergic neuron death, neuroinflammation, vascular damage, and astroglial and microglial activation. AD is a complex disorder, with >99% of all cases being sporadic and typically occuring around the age of 65. Due to this intricate nature of the disorder, experiments have limitations; however, three-dimensional organotypic brain slices may offer the best alternative for studying the mechanisms involved in the progression of AD. This review provides an overview of how to study the general aspects of AD , focusing on (a) β-amyloid plaques in brain slices, (b) tau pathology induced by chemical drugs, (c) cell death of cholinergic neurons and protection by nerve growth factor, (d) activation of astrocytes and microglia, and (e) vascular pathologies, including the role of platelets. Furthermore, we investigated (f) how microcontact printing on brain slices can be used to study the spread of β-amyloid and tau, and (g) how brain slices can help identify novel human AD biomarkers.
阿尔茨海默病（AD）是一种严重的神经退行性脑疾病，其分子特征为细胞外β-淀粉样蛋白斑块、神经元内tau神经原纤维缠结、胆碱能神经元死亡、神经炎症、血管损伤以及星形胶质细胞和小胶质细胞激活。AD是一种复杂的疾病，所有病例中>99%为散发性，通常发生在65岁左右。由于该疾病的这种复杂性，实验存在局限性；然而，三维器官型脑片可能为研究AD进展所涉及的机制提供最佳选择。本综述概述了如何研究AD的一般方面，重点关注：（a）脑片中的β-淀粉样蛋白斑块；（b）化学药物诱导的tau病理变化；（c）胆碱能神经元的细胞死亡及神经生长因子的保护作用；（d）星形胶质细胞和小胶质细胞的激活；（e）血管病理变化，包括血小板的作用。此外，我们还研究了：（f）如何利用脑片上的微接触印刷来研究β-淀粉样蛋白和tau的扩散；（g）脑片如何有助于鉴定新型人类AD生物标志物。
