“Elucidating Oxidative Damage in Primary Neuron Cultures Transfected with Tau Mutants”
Karen A. Baskerville, Lincoln University, Lincoln University, PA 19352

Neurofibrillary tangles are hallmark pathologies found in AD and other tauopathies, such as frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Tau mutant transgenic mice have been developed to study the pathological changes that occur in these diseases. An understanding of factors that contribute to the accumulation of tau in neurofibrillary tangles warrants further investigation. The central hypothesis of the PI is that oxidative damage contributes to the neurodegeneration found in tauopathies. In a parallel study to the proposed research, the PI is investigating the extent of oxidative damage in a p25 mouse model and p25-transfected primary neurons. The p25 mouse model also shows accumulation of tau. The mechanisms of oxidative stress in tau transgenic mice may potentially be similar to those in p25 mice since both models display accumulations of tau. The central hypothesis will be tested in the proposed research with the following specific aims: 1) to determine if oxidative damage adducts are co-localized with FTDP-17 tau mutant-transfected neurons in culture, and 2) to determine the extent of degeneration found in cultured mouse neurons transfected with GFP-expressing FTDP-17 tau mutant constructs with or without antioxidant treatment. Oxidative damage will be assessed in primary neurons transfected with a tau mutant by immunostaining for oxidative stress markers (specific aim 1); recovery from oxidative stress will be assessed by antioxidant treatment (specific aim 2). Counts of healthy neurons and degenerating neurons, as indicated by morphological changes in neurites, will be taken. It is anticipated that oxidative damage adducts will be found in the primary neurons transfected with FTDP-17. An undergraduate student at Lincoln University will play an instrumental role in carrying out the research.

Karen A. Baskerville, Ph.D.
Assistant Professor of Biology
Lincoln University
1570 Baltimore Pike
Lincoln University, PA 19352
Phone: (484) 365-7507
Fax: (484) 365-7906
Email: kbaskerville@lincoln.edu