Department of Biology
Charlottesville, VA 22904-4328
Pathogenic mechanisms in Alzheimer's Disease and other neurodegenerative disorders
Research in our laboratory is now focused primarily on Alzheimer?s disease (AD), the most common form of a group of neurodegenerative disorders known collectively as tauopathies. The histopathological hallmark of AD is the presence in brain of extracellular plaques of amyloid-? (A?) peptide fibrils, and intraneuronal neurofibrillary tangles, which are filaments composed of the protein, tau, and are found in all tauopathies. Despite the conspicuous appearance of plaques and tangles, a growing body of evidence points to their building blocks, A? and tau oligomers, as being the toxic molecular species that cause AD. For example, we have found that tau expression is required for several adverse effects of A? oligomers on neurons, including microtubules loss, ectopic re-rentry into the cell cycle, cytotoxicity and impaired mitochondrial activity. The goals of our work are to decipher the metabolic links that connect A? and tau to damage neurons, to define the structures and pathological properties of various types of A? and tau oligomers, and to leverage our basic science findings to develop more effective therapeutic and diagnostic tools for AD.