Throughout a freshman course on neurobiology of disease, Elaine Le was intrigued at how neuroscience delved into the mind and its interaction with the universe. She became fascinated with the many central nervous system processes that affect millions of people with neurological disorders and decided to get involved in neurobiological research. She spent the next several years working in Dr. LaFerla’s lab, looking to develop new models to better understand Alzheimer’s disease and to improve therapeutic strategies to combat the disease. After graduation, Elaine will seek to experience more fields of science and look for work in a clinical setting to observe treatment of patients outside of the laboratory.

Recent critical studies using tauopathy models suggest that the concomitant expression of endogenous murine tau may interfere with the disease progression by delaying the pathological accumulation of human tau in the brain. To understand the role of endogenous murine tau in the pathological events that occur in Alzheimer’s disease (AD) models, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice, referred to as 3xTg-AD/mtauKO mice. This new model allows us to determine the pathological interaction of murine tau in comparison with its parental line. Here, we show that 3xTg-AD mice presented higher tau loads in both soluble and insoluble fractions and increased tau hyperphosphorylation in the soluble fraction when compared with the parental 3xTg-AD/mtauKO. These results indicate that mouse tau is hyperphosphorylated and significantly co-aggregated with human tau in 3xTg-AD mice. Additionally, both transgenic models showed similar tau-phosphorylation-related kinase activity as well as comparable Aß pathology. Notably, both models exhibited equivalent cognitive dysfunction when tested on a spatial memory task, indicating that paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) increases observed in 3xTg-AD versus 3xTg-AD/mtauKO mice do not contribute to cognitive impairment.

Frank M. LaFerla School of Biological Sciences

This manuscript provides relevant insights to better understand the contribution of endogenous tau in AD pathology, and emphasizes the necessity of developing new AD models that better reproduce human AD pathological events.