Peripheral nerve impairment in a mouse model of alzheimer's disease

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 ? (A?) aggregates which can be found in peripheral tissues such as skeletal muscle. How-ever, 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 A? accumulation. We examined cholinergic innervation of skeletal muscle in adult Tg2576 and wild type mice by immu-nofluorescence labeling of tibialis anterior (TA) muscle sections using antibodies raised against neu-rofilament light chain (NFL) and acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (ChAT). Combining this histological approach with real time quantification of mRNA levels of nic-otinic 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 com-pared to wild type mice. Our study provides the first evidence of reduced cholinergic innervation of skeletal muscle in a mouse model of A? accumulation. This evidence sustains the possibility that sarcopenia in AD originates from A?-mediated cholinergic loss.