Neuropathology laboratory

Lab head: Professor Jillian Kril
Location: Discipline of Pathology, Charles Perkins Centre

Frontotemporal tauopathies: lost in translation?

Primary supervisor: Shelley Forrest

Frontotemporal lobar degeneration (FTLD) is a young-onset neurodegenerative with diverse clinical symptoms and pathology. While the distribution and severity of neuronal loss in FTLD underlies the clinical symptoms, the contribution of astrocytes and oligodendroglia, which play vital roles in maintaining neural function, are under appreciated. Both cell types abnormally aggregate phosphorylated tau, and the distribution of inclusions and cellular compartment affected differ substantially to produce distinct FTLD-tau pathological subtypes. These differences suggest a pivotal role for altered glial function in disease pathogenesis.Interestingly, a novel age-related astrogliopathy (ARTAG) has recently been described with tau-immunopositive astrocytic inclusions similar to those observed in FTLD. It has been proposed that these astrocytic inclusions may represent the earliest stages of pathological tau accumulation in astrocytes in FTLD-tau. This study will provide important insights into the molecular understanding of the distinctive FTLD-tau subtypes, the contribution of astrocytes in disease pathogenesis, and potentially discover new disease modifying targets.

 

Human postmortem tissue collected from a regional brain donor program is available to study. Using a variety of tau antibodies, RNA binding proteins and specific glial markers this study will determine the cellular properties and distribution of non-neuronal inclusions in FTLD-tau and ARTAG.

 

Techniques

Immunohistochemistry, histology, microscopy, quantification of neuropathological features and western blot.


Discipline: Pathology
Co-supervisors: Jillian Kril
Keywords: Frontotemporal dementia, Neurodegenerative Diseases, Pathology
Contact: