The La Spada laboratory applies the tools of molecular genetics, neuroscience, biochemistry, functional genomics, cell biology, pharmacology, and physiology to understand the cellular and molecular basis of neurodegenerative disease. Within the last decade, it has become clear that a key question in the neurodegenerative disease field is the selective vulnerability of different neuronal populations in the various diseases. Inherited disorders such as Huntington's disease are characterized by widespread expression of a mutant gene product throughout the central nervous system but display well circumscribed patterns of neuronal dysfunction and demise. This theme is also apparent in genetic examples of common neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and prion disease. Our basic research efforts are dedicated to understanding the basis for this selective vulnerability in different neurological disorders.