EXPRESSION OF CELL-DIVISION MARKERS IN THE HIPPOCAMPUS IN ALZHEIMERS-DISEASE AND OTHER NEURODEGENERATIVE CONDITIONS

Recent studies, showing that cell cycle-related nuclear proteins p105 and Ki-67 are associated with Alzheimer's disease (AD)-related cytoske letal pathology, suggested that these proteins, in addition to their f unctions in regulating the cell cycle, may have more specialised funct ions in the adult nervous system. In order to test this hypothesis we studied the expression of the cell cycle-related proteins Ki-67, pCNA and p53 in the hippocampi of 33 subjects, including some with PLD or o ther neurodegenerative disorders and some with no neurological disease . By immunohistochemistry we found nuclear expression of Ki-67 in all subregions of the hippocampus, with the highest levels in the dentate gyrus. Both neurons and glial cells expressed this protein. The propor tion of cells positive for Ki-67 and the distribution pattern varied c onsiderably depending on the pathological diagnosis. Neuronal nuclear expression of Ki-67 was increased in AD but was also elevated in young Down's syndrome subjects and in those with Pick's disease. Expression of this protein was therefore not AD-specific. We did not find nuclea r pCNA or p53 expressed in our patient groups. Contrary to previous st udies AD-type neurofibrillary tangles were not labelled with any of th e cell cycle markers used. The presence of nuclear Ki-67 expression in dicates that some hippocampal neurons are not in the quiescent G(0) ph ase but have re-entered the cell cycle. The absence of nuclear pCNA or p53 suggests that the cycle is arrested in G(1). The significance of our findings and their relationship to the production of neurodegenera tive cell death via an apoptotic mechanism are discussed.