Role of protein kinase B in Alzheimer's neurofibrillary pathology

Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it. Activated GSK-3 has been previously shown to be preferentially associated with ne...

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Bibliographic Details
Published in:	Acta neuropathologica Vol. 105; no. 4; pp. 381 - 392
Main Authors:	PEI, Jin-Jing, KHATOON, Sabiha, COWBURN, Richard F, GRUNDKE-IQBAL, Inge, IQBAL, Khalid, AN, Wen-Lin, NORDLINDER, Maria, TANAKA, Toshihisa, BRAAK, Heiko, TSUJIO, Ichiro, TAKEDA, Masatoshi, ALAFUZOFF, Irina, WINBLAD, Bengt
Format:	Journal Article
Language:	English
Published:	Berlin Springer 01-04-2003 Springer Nature B.V
Subjects:	Adult Aged Aged, 80 and over Alzheimer Disease - enzymology Alzheimer Disease - pathology Biological and medical sciences Blotting, Western Brain - enzymology Brain - pathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases glycogen synthase kinase 3 Glycogen Synthase Kinase 3 - metabolism Humans Huntington Disease - enzymology Huntington Disease - pathology Immunohistochemistry Isoenzymes - metabolism Kinases Male Medical sciences Medicin och hälsovetenskap Microscopy, Confocal Middle Aged Muscular system Neurofibrillary Tangles - enzymology Neurology Pathology Phosphorylation Protein-Serine-Threonine Kinases Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt tau Proteins - metabolism Human Immunohistochemistry Nervous system diseases Biochemical analysis Protein kinase B Enzyme Alzheimer disease Pathogenesis Glycogen synthase kinase-3 Transferases Neurofibrillary tangle Microtubule-associated protein tau Cerebral disorder Pathology Tau protein Protein kinase Central nervous system disease Degenerative disease Molecular biology Alzheimer's disease
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Summary:	Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it. Activated GSK-3 has been previously shown to be preferentially associated with neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brain. In the present study, we performed immunohistochemistry with an antibody to the active form of PKB in brains with different stages of neurofibrillary degeneration. We found that the amount of activated PKB (p-Thr308) increased in correlation to the progressive sequence of AT8 immunoreactivity and neurofibrillary changes assessed according to Braak's criteria. By confocal microscopy, activated PKB (p-Thr308) was found to appear in particular in neurons that are known to later develop NFTs in AD. Western blotting showed that activated PKB was increased by more than 50% in the 16,000- g supernatants of AD brains as compared with normal aged and Huntington's disease controls. This increase in PKB levels corresponded with a several-fold increase in the levels of total tau and abnormally hyperphosphorylated tau at the Tau-1 site. These studies suggest the involvement of PKB/GSK-3 signaling in Alzheimer neurofibrillary degeneration.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0001-6322 1432-0533
DOI:	10.1007/s00401-002-0657-y