Sarcopenia, a geriatric syndrome involving loss of muscle mass and strength, is often associated with the early phases of Alzheimer’s disease (AD). Pathological hallmarks of AD including amyloid β (Aβ) aggregates which can be found in peripheral tissues such as skeletal muscle. However, not much is currently known about their possible involvement in sarcopenia. We investigated neuronal innervation in skeletal muscle of Tg2576 mice, a genetic model for Aβ accumulation. We examined cholinergic innervation of skeletal muscle in adult Tg2576 and wild type mice by immunofluorescence labeling of tibialis anterior (TA) muscle sections using antibodies raised against neurofilament light chain (NFL) and acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (ChAT). Combining this histological approach with real time quantification of mRNA levels of nicotinic acetylcholine receptors, we demonstrated that in the TA of Tg2576 mice, neuronal innervation is significantly reduced and synaptic area is smaller and displays less ChAT content when compared to wild type mice. Our study provides the first evidence of reduced cholinergic innervation of skeletal muscle in a mouse model of Aβ accumulation. This evidence sustains the possibility that sarcopenia in AD originates from Aβ-mediated cholinergic loss.

中文翻译：

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阿尔茨海默病小鼠模型中的外周神经损伤

肌肉减少症是一种涉及肌肉质量和力量丧失的老年综合征，通常与阿尔茨海默病 (AD) 的早期阶段有关。AD 的病理学标志包括淀粉样蛋白 β (Aβ) 聚集体，可在骨骼肌等外周组织中发现。然而，目前对他们可能参与肌肉减少症的了解不多。我们研究了 Tg2576 小鼠骨骼肌中的神经元神经支配，这是一种 Aβ 积累的遗传模型。我们使用针对神经丝轻链 (NFL) 和乙酰胆碱 (ACh) 合成胆碱乙酰转移酶 (ChAT) 的抗体，通过胫骨前 (TA) 肌肉切片的免疫荧光标记，检测了成年 Tg2576 和野生型小鼠骨骼肌的胆碱能神经支配。将这种组织学方法与烟碱型乙酰胆碱受体 mRNA 水平的实时定量相结合，我们证明在 Tg2576 小鼠的 TA 中，与野生型小鼠相比，神经元神经支配显着减少，突触面积更小，显示的 ChAT 含量更少。我们的研究提供了在 Aβ 积累小鼠模型中骨骼肌胆碱能神经支配减少的第一个证据。该证据支持 AD 中的肌肉减少症源于 Aβ 介导的胆碱能丧失的可能性。我们的研究提供了在 Aβ 积累小鼠模型中骨骼肌胆碱能神经支配减少的第一个证据。该证据支持 AD 中的肌肉减少症源于 Aβ 介导的胆碱能丧失的可能性。我们的研究提供了在 Aβ 积累小鼠模型中骨骼肌胆碱能神经支配减少的第一个证据。该证据支持 AD 中的肌肉减少症源于 Aβ 介导的胆碱能丧失的可能性。