The purpose of this project is to determine if the locus coeruleus is more vulnerable in FTLD-tau compared to FTLD-TDP by measuring tau and TDP burden and other markers of neurodegeneration.

The locus coeruleus is a nucleus of noradrenergic cells located in the brainstem that plays a major role in arousal, cognition, and stress responses. Previous studies have suggested that the locus coeruleus is susceptible to degeneration in patients diagnosed with Parkinson’s disease and Alzheimer’s disease, but its vulnerability in frontotemporal lobar degeneration (FTLD) is not well understood.

FTLD is comprised of two main types of proteinopathies: tauopathies (FTLD-tau) and transactive response DNA-binding protein of 43kDa (FTLD-TDP), and an accurate identification of these neuropathologies in living patients is necessary for clinical trials that plan to target these abnormal protein aggregates.

Staging studies suggest that the distribution of pathology in the locus coeruleus of FTLD-Tau patients occurs at the early stages of disease progression, whereas the locus coeruleus of FTLDTDP patients remains mostly intact.

Understanding the differential progression of FTLD-TDP and FTLD-Tau pathology in specific brain regions, such as the locus coeruleus, could guide the development of biomarkers for the early detection of these disorders and possibly allow us to influence their progression.