|Budget Amount *help
¥7,000,000 (Direct Cost : ¥7,000,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1995 : ¥4,800,000 (Direct Cost : ¥4,800,000)
To clarify the relationship between amyloid beta protein deposits and phosphorylation of tau protein, the distribution of phosphorylated and non-phosphorylated tau protein is examined in the brains of various animals including non-demented aged human and patiens with Alzheimer's disease.In the brains of ageddogs, bears, monkeys, cats, camels, and sheep, phospharylated tau proteinswere distributed mainly in the oligodendrocytes, but not in the neunrons. No neurofibrillary tangles were found in the brains of these animals.Among senile plaques of these animals, phosphorylated tau prpteins were not found. On the contrary, in the brains of Alzheimer patients and non-demented aged human, apparent accumulation of phosphorylated tau protein was noted in the neurons with neurofibrillary tangles and neurites in senile plaques.These findings might suggest thatthe phosphorylation of tau protein is not depend on the presence of beta protein.but is uniqye event in the aging human brains.
An immunohistochemical study onthe constituents of senile plaques other than beta protein was performed to know the role of these proteins on thegenesis of senile plaques.Co-localization of apolipoprotein E,cystatin C,alpha 1-antichymotrypsin, cathepsin D and cathepsin B with beta protein was found in canine senile plaques with amyloid deposition.However, canine diffuse plaques thought as the initial form of senile plaques, showed immunoreactivity only for beta protein and apolipoprotein E.The number of apolipoprotein E-positive diffuse plaques is quite small as compared with that of diffuse plaques detected by beta-immunostaining.Simikarresults were also found in the brains of agedbear, monkey, cat, and camel.These findings might suggest thet apolipoprotein play a role on the aggregation of beta protein as amyloid, but does not contribute for the initial productionof beta protein. Furthermire, several proteases and protease inhibitors, will appear secondarily as the results of amyloid depostis.