Abeta amyloidosis induces the initial stage of tau accumulation in APP(Sw) mice.
To clarify how Abeta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3alpha (GSK3alpha), GSK3beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain Abeta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3beta. Smaller contributions of GSK3alpha, CDK5 and MAPK were suggested. Thus, brain Abeta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease.
Tomidokoro
Y
Y
Department of Neurology, Gunma University School of Medicine, 3-39-22 Showamachi, Maebashi, 371-8511, Gunma, Japan. tomidoko@med.gunma-u.ac.jp
Ishiguro
K
K
Harigaya
Y
Y
Matsubara
E
E
Ikeda
M
M
Park
J M
JM
Yasutake
K
K
Kawarabayashi
T
T
Okamoto
K
K
Shoji
M
M
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000201:enzymology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D015398:Signal Transduction / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011518:Proto-Oncogene Proteins; D016875:tau Proteins; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D038341:Glycogen Synthase Kinases; D051360:Cyclin-Dependent Kinase 5; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3