Development of AD-Like Pathology in Skeletal Muscle.

X Chen, N M Miller, Z Afghah, J D Geiger
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Abstract

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.

Abstract Image

骨骼肌中 AD 类病理学的发展。
针对阿尔茨海默病(AD)的有效治疗策略需要及早发现阿尔茨海默病;然而,阿尔茨海默病(AD)的临床诊断并不精确,只有通过尸检才能明确诊断出阿尔茨海默病的病理标志,包括由 Aβ 组成的老年斑和由磷酸化 tau 组成的神经纤维缠结。虽然已开发出多种生物标志物并用于临床,但没有一种生物标志物能预测 AD 的后续临床病程。因此,确定新的生物标志物以帮助诊断早期 AD、预测后续临床病程和开发新的治疗策略至关重要。鉴于在外周组织中也能检测到包括 Aβ 积累和磷酸化 tau 在内的 AD 病理学特征,AD 被认为是一种全身性疾病。由于没有血脑屏障的保护,全身性因素对外周组织的影响比大脑神经元更早。在这里,我们将讨论骨骼肌中类似 AD 病理的发展以及骨骼肌活检(检查 Aβ 积累和磷酸化 tau)作为 AD 生物标记物的潜在用途。
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