The P53 Homologue P73 Accumulates in the Nucleus and Localizes to Neurites and Neurofibrillary Tangles in Alzheimer Disease Brain

The molecular mechanisms that regulate neuronal survival vs. death during Alzheimer disease (AD) remain unclear. Nonetheless, a number of recent studies indicate that increased expression or altered subcellular distribution of numerous cell cycle proteins during AD may contribute to disease pathogenesis. Because homologues of p53, a key regulatory protein in the cell cycle, such as p73, have been identified and shown to participate in cellular differentiation and death pathways, we examined the expression and distribution of p73 in the hippocampus of eight control and 16 AD subjects. In control subjects, hippocampal pyramidal neurones exhibit p73 immunoreactivity that is distributed predominately in the cytoplasm. In AD hippocampus, increased levels of p73 are located in the nucleus of pyramidal neurones and p73 is located in dystrophic neurites and cytoskeletal pathology. Immunoblot analysis confirmed the presence of p73 in the hippocampus. These data indicate that p73 is expressed within hippocampal pyramidal neurones and exhibits altered subcellular distribution in AD.