Immunocytochemistry of tau phosphoserine 413 and tau protein kinase I in Alzheimer pathology.
One unique phosphorylation site consistently found in paired helical filament tau, serine 413, is modified by tau protein kinase I/glycogen synthase kinase-3 beta but no other known tau kinase. Here we present immunocytochemistry from Alzheimer's disease brains showing that focal subpopulations of hippocampal CA1 pyramidal neurons and neuritic plaques are strongly reactive for tau protein kinase I/glycogen synthase kinase-3 beta and tau phosphoserine 413 in early stages of pathology. Colocalization of these epitopes suggests that tau protein kinase I/glycogen synthase kinase-3 beta abnormally phosphorylates tau and is in a position to disrupt neuronal metabolism in anatomical areas vulnerable to Alzheimer's disease.
Shiurba
R A
RA
Laboratories for Molecular Neuroscience, McLean Hospital, Harvard Medical School, Belmont, MA 02178, USA.
Ishiguro
K
K
Takahashi
M
M
Sato
K
K
Spooner
E T
ET
Mercken
M
M
Yoshida
R
R
Wheelock
T R
TR
Yanagawa
H
H
Imahori
K
K
Nixon
R A
RA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology / Q000201:enzymology; D018604:Epitope Mapping; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000737:chemistry / Q000201:enzymology; D007536:Isomerism; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000201:enzymology; D010455:Peptides / Q000276:immunology; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017966:Pyramidal Cells / Q000201:enzymology / Q000473:pathology; D016875:tau Proteins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology
D010455:Peptides; D016875:tau Proteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase