IMMUNOREACTIVITY OF THE NUCLEAR ANTIGEN P105 IS ASSOCIATED WITH PLAQUES AND TANGLES IN ALZHEIMERS-DISEASE

BACKGROUND: The protein p105 is a nuclear antigen associated with cell proliferation. Recent investigations have indicated that many molecul es previously considered to be growth-associated are actually involved in plasticity of the central nervous system. EXPERIMENTAL DESIGN: For the present study, using immunohistochemical and immunochemical techn iques in control and Alzheimer's disease (AD) brain, we explored the p ossibility that p105 could be involved in the aberrant sprouting respo nse. AD tissue was used because in this disorder, the neuronal sprouti ng processes display a disruption in their cytoskeleton and the microt ubule-associated protein, tau is abnormally phosphorylated. Control ex periments were performed with the p105 antibody from an independent so urce, and with an antibody against Ki67. RESULTS: The antibody against p105 (but not against Ki-67) immunolabeled the tangles, neuropil thre ads, and a subpopulation of fusiform neurites in the plaque. The p105 immunoreactivity was colocalized with tau and the numbers of tangles i mmunostained with p105 antibody correlated with the number of tangles immunolabeled with an antibody against tau. Western blot analysis of h uman brain homogenates showed that the antibody against p105 immunosta ined a major band at an estimated molecular weight of 105 kilodaltons and a secondary band at 84 kilodaltons. In AD frontal cortex, there wa s a significant increase in the 84 kilodalton band in the particulate, but not in the cytosolic fraction. CONCLUSIONS: The characterization of the patterns of expression of this class of nuclear antigen in the brain might provide important clues as to the mechanisms of plasticity and abnormal growth under normal conditions, as well as in AD.