Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Endocrine, Liyuan Hospital, Key Laboratory of Ministry of Education for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China.
Transl Neurodegener. 2024 Sep 4;13(1):45. doi: 10.1186/s40035-024-00432-x.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized pathologically by extracellular deposition of β-amyloid (Aβ) into senile plaques and intracellular accumulation of hyperphosphorylated tau (pTau) as neurofibrillary tangles. Clinically, AD patients show memory deterioration with varying cognitive dysfunctions. The exact molecular mechanisms underlying AD are still not fully understood, and there are no efficient drugs to stop or reverse the disease progression. In this review, we first provide an update on how the risk factors, including APOE variants, infections and inflammation, contribute to AD; how Aβ and tau become abnormally accumulated and how this accumulation plays a role in AD neurodegeneration. Then we summarize the commonly used experimental models, diagnostic and prediction strategies, and advances in periphery biomarkers from high-risk populations for AD. Finally, we introduce current status of development of disease-modifying drugs, including the newly officially approved Aβ vaccines, as well as novel and promising strategies to target the abnormal pTau. Together, this paper was aimed to update AD research progress from fundamental mechanisms to the clinical diagnosis and therapies.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其病理学特征为β-淀粉样蛋白（Aβ）在老年斑中外泌沉积和过度磷酸化的 tau（pTau）在内质网中积累形成神经纤维缠结。临床上，AD 患者表现为记忆恶化，伴有不同程度的认知功能障碍。AD 的确切分子机制仍不完全清楚，也没有有效的药物可以阻止或逆转疾病进展。在这篇综述中，我们首先提供了最新的信息，介绍了包括 APOE 变体、感染和炎症在内的风险因素如何导致 AD；Aβ和 tau 如何异常积累以及这种积累如何在 AD 神经退行性变中发挥作用。然后我们总结了常用于 AD 的实验模型、诊断和预测策略以及从 AD 高危人群外周生物标志物的进展。最后，我们介绍了目前疾病修饰药物的开发状况，包括最近正式批准的 Aβ疫苗，以及针对异常 pTau 的新型有前途的策略。总之，本文旨在从基础机制到临床诊断和治疗，更新 AD 的研究进展。
