Cell cycle-associated
nuclear proteins may have more specialized functions in the adult nervous system in addition to those directly associated with cell proliferation, as suggested by a recent study showing that neurofibrillary tangles (NFT) and dystrophic neurites in
Alzheimer's disease (AD) are immunoreactive for the proliferation-associated
antigen p105. To further investigate this hypothesis, we studied the expression of another proliferation-associated
antigen, Ki-67, in the brains of patients with AD and other
neurodegenerative disorders.
Formalin-fixed,
paraffin-embedded sections from autopsy cases of AD,
Down's syndrome with
dementia and AD pathology (DS/AD),
Pick's disease (PiD),
progressive supranuclear palsy (PSP),
Lewy body disease (LBD),
Parkinson's disease (PD),
corticobasal degeneration (CBD), and young and aged normal brains, and from two surgically resected
gangliogliomas were immunostained using
antibodies to Ki-67 (MIB-1 clone equivalent) and tau (tau). Ki-67 staining was performed following
antigen retrieval by microwave heating. Ki-67 labeled NFT that were observed in the AD, DS/AD, PiD, PSP, LBD, and PD cases, one aged normal brain, and one
ganglioglioma. Ki-67 generally labeled fewer NFT compared to tau. Pick bodies, ballooned neurons (Pick cells) in CBD and PiD, and nigral corticobasal inclusions in CBD were immunoreactive for tau but not Ki-67. Neither antibody labeled cortical or subcortical Lewy bodies. Our findings suggest that Ki-67 may be involved in the pathogenesis of neurofibrillary 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 susceptible neurons.