466Loss of neocortical choline acetyltransferase activity correlates with disease severity but not non-cognitive symptoms in Alzheimer's disease

Alzheimer’s disease (AD) is characterized by memory decline, but is often associated with non-cognitive symptoms, including muscular dysfunction. In the majority of cases these motor disturbances are seen when other neuro-degenerative disorders such as Parkinson’s disease overlap dementia, however these can also be directly related to AD itself. Although the patho-mechanism remains largely unclear, β-amyloid peptide (βAP) is thought to be a key role-player in both the brain and periphery. Here we studied the electro-genesis of skeletal muscle fibers in a mouse transgenic AD model. Membrane potential was recorded by standard electro-physiological techniques. Compared to wild-type rodents, AD mice show severe disturbances in skeletal muscle electro-genesis manifested by significant depolarization of myo-fibers. These changes are not affected by short-term βAP treatment, the mark of a chronic degenerative process in the periphery directly related to AD whereby ion pumps on muscle membranes exhibit reduced activity. This phenomenon may explain ionic imbalance and cellular dysfunction both in the neuro-muscular system and in the brain. The observed motor disturbances might play a key role in impaired activities of daily living, and addressing the muscular patho-physiology could improve quality of life in AD.