Characterising brainstem neurons undergoing tauopathy

The assembly and stabilisation of microtubules in neurons is regulated by protein tau. Mutations in the tau gene lead to the accumulation of hyperphosphorylated tau as neurofibrillary tangles, which are pathological hallmarks of neurodegenerative diseases such as frontotemporal dementia, Alzheimer’s disease and progressive supranuclear palsy.


1. Characterise the distribution of neurons undergoing tauopathy in the brainstem of Tau-P301L mice prior to, and following, the emergence of behavioural abnormalities; and
2. Identify the chemical phenotypes of neurons undergoing tauopathy.

Early assessments of a mouse model of tauopathy carrying a P301L mutation in the tau gene identified defects in autonomic functions, including respiration and swallowing, as well as decreased ambulation and balance abnormalities. Coinciding with the progressively deteriorating behavioural and autonomic functions is the emergence of severe tauopathy in neurons of the brainstem (see Figure).

Paired helical filament-Tau immunoreactivity in Tau-P301L mice that displayed movement and gait disturbances. (A) Cuneiform nucleus (CnF) in the midbrain. (B) Gigantocellular reticular nucleus (Gi) in the medulla. (C) Vestibular nuclei (Ve) in the brainstem and lateral cerebellar nucleus (Lat).

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