Severe tauopathy and axonopathy in the medulla oblongata in Alzheimer’s disease implicate the changes in autonomic nervous function

Abstract

The autonomic dysfunctions in Alzheimer’s disease (AD) have been identified from many clinical studies, however, there is still a lack of evidence directly verifying the structural abnormalities of the autonomic nervous system in AD. Human medulla oblongatas from four AD patients or five non-AD subjects were obtained and observed by using immunohistochemical staining of hyperphosphorylated tau and Aβ amyloid, and post-mortem tracing techniques. We found distinct axonal and somatic immunoreactivities for the tau markers AT8 and Tau-5 in the different areas of the medulla oblongata in AD patients, which was particularly obvious in the dorsal nucleus of the vagus nerve, the nucleus of the solitary tract and the reticular nucleus. The swollen axons, which are a typical feature of axonopathy, were not only identified in the axons with immunohistochemical labeling of AT8 and Tau-5 in the different nuclei of the medulla oblongata, but also in the tracer-labeled afferent and efferent fibres of the vagus nerve in AD patients. Such changes in tauopathy and axonopathy were only occasionally found in the non-AD aged subjects. Interestingly, we did not observe any intra- or extracellular Aβ deposits in the medulla oblongatas of the AD patients or of the non-AD subjects. These results in small samples suggest that occurrence of tauopathy and axonopathy in the parasympathetic nuclei of the medulla oblongata in AD patients may implicate the change of autonomic nervous function.