The traditional classification of neurodegenerative disorders into discrete diseases has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. A clinical continuum is particularly notable for neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins. Patients can have a mixture of cognitive, language, and motor symptoms. Examples of these disorders include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), primary progressive aphasia (PPA), and HD-negative Huntington. Some causative genes have been found for each disorder, although most patients have sporadic disease. Interestingly, the same genetic mutation can produce different clinical phenotypes. The link between the gene mutations and pathology in these disorders may lie in the molecular and cellular processes affected by mutant gene products. As the field of neurology moves more towards the molecular characterization of neurodegenerative disorders, there is a need to understand clinical phenomenology in the context of pathology and genetic or epigenetic defects that are the drivers of disease. Given the broad spectrum of neurological symptoms in this family of disorders, the goal of this clinic is to bring together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. The objective is to gain knowledge that will set the stage for precision medicine in which therapy will be tailored to the underlying cause of each patient's disease. Considerable work was carried out during FY17 to prepare for the clinic, including hiring a nurse practitioner, obtaining IRB approval to carry out clinical screening and collection of biospecimens on patients with neurodegenerative disorders, staff training, and establishing case report forms, recruitment materials, and an electronic data system. In FY18, enrollment of patients began in a monthly screening clinic. Clinical staff also provided support for two ongoing protocols. The clinic holds a monthly conference for the neurologists, neuropsychologists, and health personnel involved in the clinic to discuss individual patients and arrive at a consensus.
