TDP43-Positive Intraneuronal Inclusions in a Patient with Motor Neuron Disease and Parkinson's Disease

Background: The role of the 43-kDa transactivation-responsive DNA-binding protein (TDP43) in neurodegenerative diseases is not yet clearly established. Objective: To assess for the first time the presence of TDP43 in a patient with motor neuron disease (MND) and Parkinson's disease (PD). Methods: A 78-year-old woman developed poorly dopa-responsive parkinsonism without cognitive alteration. Three years later, MND appeared and led to death in less than a year. Neuropathologic examination was performed. Results: We observed the presence of PD and MND lesions with TDP43-positive cytoplasmic inclusions in the spinal cord and bulbar nuclei but not in the dentate gyrus and neocortex. The MND was characterized by a severe degeneration of bulbar and cervical lower motor neurons. Numerous senile plaques and topographically limited neurofibrillary tangles were also observed. Conclusion: The mechanisms underlying the rare co-occurrence of PD and MND are still unclear. The assessment of an abnormal reactivity for TDP43 in our case might gain more insight into the pathophysiology of this association of two diseases. Further studies are needed to confirm these findings and to understand the role of TDP43 in neurodegenerative diseases. Copyright (C) 2010 S. Karger AG, Basel