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引用次数: 0
摘要
阿尔茨海默病(AD)是最常见的神经退行性疾病,病理特征是细胞外β淀粉样蛋白(Aβ)沉积成老年斑,细胞内高磷酸化tau(pTau)堆积成神经纤维缠结。临床上,注意力缺失症患者会出现记忆力衰退和各种认知功能障碍。目前,人们仍未完全了解导致注意力缺失症的确切分子机制,也没有有效的药物来阻止或逆转疾病的发展。在这篇综述中,我们首先介绍了APOE变异、感染和炎症等风险因素如何导致AD;Aβ和tau如何异常累积,以及这种累积如何在AD神经变性中发挥作用。然后,我们总结了常用的实验模型、诊断和预测策略,以及来自 AD 高危人群的外周生物标记物的进展。最后,我们介绍了改变疾病的药物的研发现状,包括新近正式批准的 Aβ 疫苗,以及针对异常 pTau 的新颖且有前景的策略。总之,本文旨在更新从基础机制到临床诊断和治疗的AD研究进展。
Updates in Alzheimer's disease: from basic research to diagnosis and therapies.
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.
期刊介绍:
Translational Neurodegeneration, an open-access, peer-reviewed journal, addresses all aspects of neurodegenerative diseases. It serves as a prominent platform for research, therapeutics, and education, fostering discussions and insights across basic, translational, and clinical research domains. Covering Parkinson's disease, Alzheimer's disease, and other neurodegenerative conditions, it welcomes contributions on epidemiology, pathogenesis, diagnosis, prevention, drug development, rehabilitation, and drug delivery. Scientists, clinicians, and physician-scientists are encouraged to share their work in this specialized journal tailored to their fields.