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Movement disturbances in frontotemporal dementia

Movement disorders are complications that occur in a number of neurodegenerative diseases, including e.g. Parkinson’s disease, motor neuron disease and a subset of patients affected by frontotemporal dementia, and symptoms can include a progressive decrease in ambulation, deteriorating gait and decline in posture.

Aims

1. Identify the onset of movement disturbances in individual Tau-P301L mice using movement-specific behavioural tests;
2. Outline the timeline of the progressive worsening of movement deterioration, from onset to development of severe movement disorders; and
3. Characterise the presence of tauopathy and neurodegeneration in movement/gait-related brain regions (see Figure 1).

This project examines the onset and progression of movement disorders using a mouse model of frontotemporal dementia bearing the Tau-P301L mutation. We know this mouse model develops severe movement disorders, but their onset is not uniform and can occur at any time point between 6-12 months of age (mimicking the situation in humans suffering frontotemporal dementia in which first diagnosis can occur in the mid 20s and up to the early 70s).

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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