Immunoreactivity of the nuclear antigen p105 is associated with plaques and tangles in Alzheimer's disease.
BACKGROUND
The protein p105 is a nuclear antigen associated with cell proliferation. Recent investigations have indicated that many molecules previously considered to be growth-associated are actually involved in plasticity of the central nervous system.


METHODS
For the present study, using immunohistochemical and immunochemical techniques in control and Alzheimer's disease (AD) brain, we explored the possibility that p105 could be involved in the aberrant sprouting response. AD tissue was used because in this disorder, the neuronal sprouting processes display a disruption in their cytoskeleton and the microtubule-associated protein, tau is abnormally phosphorylated. Control experiments were performed with the p105 antibody from an independent source, and with an antibody against Ki-67.


RESULTS
The antibody against p105 (but not against Ki-67) immunolabeled the tangles, neuropil threads, and a subpopulation of fusiform neurites in the plaque. The p105 immunoreactivity was colocalized with tau and the numbers of tangles immunostained with p105 antibody correlated with the number of tangles immunolabeled with an antibody against tau. Western blot analysis of human brain homogenates showed that the antibody against p105 immunostained a major band at an estimated molecular weight of 105 kilodaltons and a secondary band at 84 kilodaltons. In AD frontal cortex, there was 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.
Masliah
E
E
University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla.
Mallory
M
M
Alford
M
M
Hansen
L A
LA
Saitoh
T
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D034961:Antigens, Nuclear; D015153:Blotting, Western; D001923:Brain Chemistry; D002455:Cell Division; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D016501:Neurites / Q000737:chemistry / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis / Q000276:immunology; D016160:Retinoblastoma Protein / Q000032:analysis* / Q000276:immunology*; D016875:tau Proteins / Q000032:analysis
D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D016875:tau Proteins