Tauopathy Induced Progressive Cell Loss of FoxP2‐Expressing Neurons in the Kölliker‐Fuse nuclei (KFn) is Tightly Linked to Clinically Relevant Laryngeal Dysfunction in Tau‐P301L Mice

The developmental transcription factor FoxP2 is a highly reliable marker for the pontine KFn. The KFn have important function in the control of laryngeal adductor function during breathing and during a variety of upper airway motor behavior (e.g swallowing, vocalization). Immunohistochemistry for FoxP2 and hyperphosphorylated Tau protein in an established mouse model of tauopathy (Tau P‐301L) indicates: (i) early onset tauopathy (age 3–5 months) occurs in the KFn region of otherwise non‐symptomatic Tau‐P301L mice; (ii) early KFn tauopathy can be identified before the onset of severe cognitive and/or motor dysfunction by an impaired sniff pattern in plethysmographic recordings in awake animals after exposure to trigeminal and non‐trigeminal odors (n=18); (iii) with aging, a progressive cell loss of FoxP2‐expressing neurons of the KFn can be detected. At terminal stages of 8–9 months old Tau‐P301L, a high percentage of the FoxP2‐expressing cells disappeared. The progressive cell loss in KFn correlates with emerging laryngeal dysfunctions which are in particular expressed as a dysphagia phenotype. As reported previously also the breathing pattern indicates progressively shows paradoxical inspiratory laryngeal adduction (Dutschmann et al., 2010). WE conclude that tauopathy linked neurodegeneration of KFn neurons may significantly contribute to upper airway disorders such as dysphagia mutism and paradoxical vocal cord motion seen in a variety of neurodegenerative diseases such as Alzheimer's disease Parkinsonism, frontotemporal dementia and motor neuron disease. Support or Funding Information The work was supported by ARC future fellowship and the Florey Institute for Neuroscience and Mental Health