Casein kinase II alteration precedes tau accumulation in tangle formation.
Previous studies have shown altered casein kinase II (CK-II) in Alzheimer's disease (AD). For the present study, the authors analyzed CK-II immunoreactivity at various stages of tangle formation using quantitative laser confocal microscopy and immunoelectron microscopy. AD hippocampal pyramidal cells without neurofibrillary tangles (NFTs) displayed 15% more anti-tau immunoreactivity (P less than 0.01) and 43% more anti-CKII immunolabeling than controls (P less than 0.001). In AD, tangle-bearing hippocampal neurons with strong anti-tau immunoreactivity (threefold increase from controls) showed a significant 22% increase in anti-CKII immunolabeling (P less than 0.01), compared with those without NFTs. Neurons with early neurofibrillary changes showed diffuse anti-CKII immunostaining in their cytoplasm and cell processes. In tangle-bearing neurons, in which a higher level of tau immunoreactivity was detected, anti-CKII immunolabeling was distributed along a fibrillar meshwork in cell bodies and processes. Linear regression analysis of anti-CKII and anti-tau immunoreactivity in AD showed a positive correlation (r = 0.53, P less than 0.001). At the ultrastructural level, anti-CKII was immunolocalized to the paired helical filaments (PHF) of the tangle-bearing neurons, as well as to PHF in neuropil threads and some dystrophic neurites in plaques. These results suggest a possible role for CK-II in tangle formation.
Masliah
E
E
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093-0624.
Iimoto
D S
DS
Mallory
M
M
Albright
T
T
Hansen
L
L
Saitoh
T
T
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001344:Autopsy; D047390:Casein Kinase II; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases