Tartaglia, Maria Carmela
University Health Network (Toronto)
Multimodal Assessment For Predicting Specific Pathological Substrate in Frontotemporal Lobar Degeneration
Frontotemporal dementia (FTD) is the most common cause of dementia before the age of 60. It is characterized by progressive impairment of behavior (behavioral variant FTD or bvFTD) or language (primary progressive aphasia or PPA). Three other clinical entities strongly linked to FTD at a clinical and pathological level are corticobasal syndrome (CBS), progressive supranuclear palsy (PSP) and FTD-Motor neuron disease. Frontotemporal lobar degeneration (FTLD), the underlying pathology responsible for the different clinical syndromes is heterogeneous with molecular abnormalities in three different proteins implicated: Tau, TDP-43 and Fused in Sarcoma (FUS). It is difficult to predict the underlying pathology in many of these syndromes but the emergence of protein-specific treatments warrants accurate diagnosis of the clinical syndrome as well as the causative protein. Although some syndromes are more often associated with one protein abnormality, in many cases, it is still impossible to predict the underlying pathology with certainty. With the development of a Positron Emission Tomography (PET) Tau ligand, it will be possible to diagnose Tau invivo. Unfortunately, PET is not readily available and the relationship between PET Tau binding and MRI as well as cerebrospinal fluid levels of neurodegenerative markers is unknown. The overall goal of this project is to use a multimodal approach that includes clinical, neuroimaging and cerebrospinal fluid data to predict the underlying pathology and thus guide treatment.