Chen X, Miller N M, Afghah Z, Geiger J D
Department of Biomedical Sciences, University of North Dakota, USA.
J Parkinsons Dis Alzheimers Dis. 2019;6(1). doi: 10.13188/2376-922x.1000028. Epub 2019 Apr 2.
Effective therapeutic strategy against Alzheimer's disease (AD) requires early detection of AD; however, clinical diagnosis of Alzheimer's disease (AD) is not precise and a definitive diagnosis of AD is only possible via postmortem examination for AD pathological hallmarks including senile plaques composed of Aβ and neuro fibrillary tangles composed of phosphorylated tau. Although a variety of biomarker has been developed and used in clinical setting, none of them robustly predicts subsequent clinical course of AD. Thus, it is essential to identify new biomarkers that may facilitate the diagnosis of early stages of AD, prediction of subsequent clinical course, and development of new therapeutic strategies. Given that pathological hallmarks of AD including Aβaccumulation and the presence of phosphorylated tau are also detected in peripheral tissues, AD is considered a systemic disease. Without the protection of blood-brain barrier, systemic factors can affect peripheral tissues much earlier than neurons in brain. Here, we will discuss the development of AD-like pathology in skeletal muscle and the potential use of skeletal muscle biopsy (examination for Aβaccumulation and phosphorylated tau) as a biomarker for AD.
针对阿尔茨海默病(AD)的有效治疗策略需要对AD进行早期检测;然而,阿尔茨海默病(AD)的临床诊断并不精确,只有通过尸检检查AD的病理特征,包括由Aβ组成的老年斑和由磷酸化tau组成的神经原纤维缠结,才能对AD做出明确诊断。尽管已经开发了多种生物标志物并在临床环境中使用,但它们都不能可靠地预测AD的后续临床病程。因此,识别可能有助于AD早期诊断、预测后续临床病程以及开发新治疗策略的新生物标志物至关重要。鉴于在周围组织中也检测到AD的病理特征,包括Aβ积累和磷酸化tau的存在,AD被认为是一种全身性疾病。在没有血脑屏障保护的情况下,全身因素对外周组织的影响要比大脑中的神经元早得多。在这里,我们将讨论骨骼肌中AD样病理的发展以及骨骼肌活检(检测Aβ积累和磷酸化tau)作为AD生物标志物的潜在用途。