Riching Andrew S, Major Jennifer L, Londono Pilar, Bagchi Rushita A
Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
ACS Pharmacol Transl Sci. 2019 Dec 3;3(1):21-28. doi: 10.1021/acsptsci.9b00091. eCollection 2020 Feb 14.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting millions worldwide. Currently, there are only four approved treatments for AD, which improve symptoms modestly. AD is believed to be caused by the formation of intercellular plaques and intracellular tangles in the brain, but thus far all new drugs which target these pathologies have failed clinical trials. New research highlights the link between AD and Type II Diabetes (T2D), and some believe that AD is actually a brain specific form of it termed Type III Diabetes (T3D). Drugs which are currently approved for the treatment of T2D, such as metformin, have shown promising results in improving cognitive function and even preventing the development of AD in diabetic patients. Recent studies shed light on the relationship between the brain and cardiovascular system in which the brain and heart communicate with one another via the vasculature to regulate fluid and nutrient homeostasis. This line of research reveals how the brain-heart axis regulates hypertension and diabetes, both of which can impact cognitive function. In this review we survey past and ongoing research and clinical trials for AD, and argue that AD is a complex and systemic disorder which requires comprehensive approaches beyond the brain for effective prevention and/or treatment.
阿尔茨海默病(AD)是一种使人衰弱的神经退行性疾病,影响着全球数百万人。目前,AD仅有四种获批的治疗方法,只能适度改善症状。人们认为AD是由大脑中细胞间斑块和细胞内缠结的形成所引起的,但迄今为止,所有针对这些病变的新药都在临床试验中失败了。新的研究突出了AD与2型糖尿病(T2D)之间的联系,一些人认为AD实际上是其一种大脑特异性形式,称为3型糖尿病(T3D)。目前获批用于治疗T2D的药物,如二甲双胍,在改善认知功能甚至预防糖尿病患者发生AD方面已显示出有前景的结果。最近的研究揭示了大脑与心血管系统之间的关系,其中大脑和心脏通过脉管系统相互沟通以调节液体和营养物质的稳态。这一系列研究揭示了脑-心轴如何调节高血压和糖尿病,而这两者都会影响认知功能。在本综述中,我们调查了过去和正在进行的AD研究及临床试验,并认为AD是一种复杂的全身性疾病,需要超越大脑的综合方法来进行有效的预防和/或治疗。