Dr. Bloom's 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 Ã?-amyloid 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, Ã?-amyloid 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 Ã?-amyloid oligomers on neurons, including microtubules loss, ectopic re-rentry into the cell cycle and cytotoxicity. The goals of our work are to decipher the metabolic links that connect Ã?-amyloid and tau to damage neurons, to define the structures and pathological properties of various types of Ã?-amyloid and tau oligomers, and to develop effective therapeutic and diagnostic tools for AD.
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