KI-67 IMMUNOREACTIVITY IN ALZHEIMERS-DISEASE AND OTHER NEURODEGENERATIVE DISORDERS

Cell cycle-associated nuclear proteins may have more specialized funct ions in the adult nervous system in addition to those directly associa ted with cell proliferation, as suggested by a recent study showing th at neurofibrillary tangles (NFT) and dystrophic neurites in Alzheimer' s disease (AD) are immunoreactive for the proliferation-associated ant igen p105. To further investigate this hypothesis, we studied the expr ession of another proliferation-associated antigen, Ki-67, in the brai ns of patients with AD and other neurodegenerative disorders. Formalin -fixed, paraffin-embedded sections from autopsy cases of AD, Down's sy ndrome with dementia and AD pathology (DS/AD), Pick's disease (PiD), p rogressive supranuclear palsy (PSP), Lewy body disease (LED), Parkinso n's disease (PD), corticobasal degeneration (CBD), and young and aged normal brains, and from two surgically resected gangliogliomas were im munostained using antibodies to Ki-67 (MIB-1 clone equivalent) and tau (tau). Ki-67 staining was performed following antigen retrieval by mi crowave heating. Ki-67 labeled NFT that were observed in the AD, DS/AD , PID, PSP, LED, and PD cases, one aged normal brain, and one gangliog lioma. Ki-67 generally labeled fewer NFT compared to tau. Pick bodies, ballooned neurons (Pick cells) in CBD and PiD, and nigral corticobasa l inclusions in CBD were immunoreactive for tau but not Ki-67. Neither antibody labeled cortical or subcortical Lewy bodies. Our findings su ggest that Ki-67 may be involved in the pathogenesis of neurofibrillar y degeneration in AD, other neurodegenerative disorders, normal aging, and neoplasms such as ganglioglioma. We postulate a possible role for Ki-67 in the production of the abnormally phosphorylated tau protein that leads to the formation of paired helical filaments within suscept ible neurons.