Khin Win’s advice to students interested in conducting research is to “be optimistic.” Her optimism has helped her keep an open mind through her research—seeing even unexpected results as valuable information. She is particularly interested in Alzheimer’s Disease and its gradual degradation of human ability and dignity. She hopes that her research may help with future understanding of this disease. In addition, she expects her research experience to help her become more knowledgeable in patient care as she moves on to medical school in the Fall of 2006. In her spare time, Khin enjoys meditation and swimming.

Neurofibrillary tangles (NFTs) are intraneuronal accumulations of fibrillar proteins—composed of hyperphosphorylated tau protein—found in several neurodegenerative diseases, including Alzheimer’s disease. Rodents have been used to study NFT pathology, but significant differences exist between human and rodent tau. This research aims to characterize the expression of tau variants (isoforms) in cultured human cortical neurons (HCNs) grown on two substrates commonly used to stimulate neuronal attachment and growth in vitro. The goal is to establish an experimental model to study molecular mechanisms involving tau in neurodegenerative diseases. Since tau plays a role in early neuronal development, we monitored neurite outgrowth during active neurite elongation. We analyzed the subcellular distribution of tau, quantified the length of neuronal extensions, and characterized the expression of tau variants. Results indicate that tau becomes progressively compartmentalized in axons during neuronal development, and that laminin significantly stimulates neurite extension. We found that all six isoforms of tau in the adult human brain are expressed in HCNs growing on both PLL and laminin substrates. Tau isoforms with four microtubule-binding tandem repeats near the carboxy terminus are subject to developmental regulation and modulation by laminin. Thus, HCNs in culture may represent a useful model for studies of tau pathology and NFT formation.

Jorge A. Busciglio School of  Biological Sciences

The quest for effective therapies to treat Alzheimer’s disease (AD) is one of the major scientific challenges faced by biomedical investigators. To achieve this goal, development of appropriate experimental models is critical to determining the molecular mechanisms relevant to the disease process. In this study, Khin Win used human cortical neurons, one of the main cell types affected in AD, to characterize the changes in the expression of tau protein variants in response to environmental cues (e.g. extracellular matrix molecules). These results represent a first step in further characterizing the modifications in tau that lead to neurofibrillary pathology in AD. Undergraduates obtain numerous benefits from participating in independent research, most notably the value of teamwork and the discovery of their own potential as future researchers and/or health care providers.