Dr. Holsinger’s research interests surround understanding molecular mechanisms underlying neurodegenerative diseases with a particular focus on Alzheimer’s disease and the -secretase cleaving enzyme (BACE1). This enzyme initiates the generation of amyloid-beta (A), accumulation of which leads to its deposition as amyloid plaques, a pathological feature of Alzheimer’s. Following seminal discoveries of increased BACE1 in the brain and cerebrospinal fluid of Alzheimer’s subjects, the laboratory focuses on identifying mechanisms that lead to increased levels of BACE1 and those that regulate its transcription. Dr. Holsinger’s research also focuses on neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF) and its expression in the diseased brain with an aim to regulating levels of these factors for therapeutic benefit. As part of this drive, Holsinger and colleagues employ techniques such as neuromodulation and piezoelectricity to regulate gene and protein expression in tissue and cells.