Kelliny Sally, Zhou Xin-Fu, Bobrovskaya Larisa
Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Faculty of Pharmacy, Assiut University, Assiut, Egypt.
J Neurosci Res. 2025 May;103(5):e70046. doi: 10.1002/jnr.70046.
Alzheimer's disease (AD) is a devastating form of dementia, with the number of affected individuals rising sharply. The main hallmarks of the disease include amyloid-beta plaque deposits and neurofibrillary tangles consisting of hyperphosphorylated tau protein, besides other pathological features that contribute to the disease's complexity. The causes of sporadic AD are multifactorial and mostly age-related and involve risk factors such as diabetes and cardiovascular or cerebrovascular disorders. Frontotemporal dementia (FTD) is another type of dementia characterized by a spectrum of behaviors, memory, and motor abnormalities and associated with abnormal depositions of protein aggregation, including tau protein. Currently approved medications are symptomatic, and no disease-modifying therapy is available to halt the disease progression. Therefore, the development of multi-targeted therapeutic approaches could hold promise for the treatment of AD and other neurodegenerative disorders, including tauopathies. In this article, we will discuss the pathophysiology of AD and FTD, the proposed hypotheses, and current therapeutic approaches, highlighting the development of novel drug candidates and the progress of clinical trials in this field of research.
阿尔茨海默病（AD）是一种毁灭性的痴呆症，受影响的个体数量正在急剧上升。该疾病的主要特征包括β-淀粉样蛋白斑块沉积和由高度磷酸化的tau蛋白组成的神经原纤维缠结，此外还有其他导致疾病复杂性的病理特征。散发性AD的病因是多因素的，主要与年龄相关，涉及糖尿病、心血管或脑血管疾病等风险因素。额颞叶痴呆（FTD）是另一种痴呆症，其特征是一系列行为、记忆和运动异常，并与蛋白质聚集物（包括tau蛋白）的异常沉积有关。目前批准的药物只是对症治疗，尚无疾病修饰疗法可阻止疾病进展。因此，多靶点治疗方法的开发有望用于治疗AD和其他神经退行性疾病，包括tau蛋白病。在本文中，我们将讨论AD和FTD的病理生理学、提出的假说以及当前的治疗方法，重点介绍新型候选药物的开发以及该研究领域临床试验的进展。
