Phosphorylation of soluble tau differs in Pick's disease and Alzheimer's disease brains.
Frontotemporal lobar degeneration (FTLD) is a common cause of presenile dementia characterised by behavioural and language disturbances. Pick's disease (PiD) is a subtype of FTLD, which presents with intraneuronal inclusions consisting of hyperphosphorylated tau protein aggregates. Although Alzheimer's disease (AD) is also characterised by tau lesions, these are both histologically and biochemically distinct from the tau aggregates found in PiD. What determines the distinct characteristics of these tau lesions is unknown. As phosphorylated, soluble tau has been suggested to be the precursor of tau aggregates, we compared both the level and phosphorylation profile of tau in tissue extracts of AD and PiD brains to determine whether the differences in the tau lesions are reflected by differences in soluble tau. Levels of soluble tau were decreased in AD but not PiD. In addition, soluble tau was phosphorylated to a greater extent in AD than in PiD and displayed a different phosphorylation profile in the two disorders. Consistently, tau kinases were activated to different degrees in AD compared with PiD. Such differences in solubility and phosphorylation may contribute, at least in part, to the formation of distinct tau deposits, but may also have implications for the clinical differences between AD and PiD.
van Eersel
Janet
J
Discipline of Pathology, The University of Sydney, Sydney, NSW, 2006, Australia.
Bi
Mian
M
Ke
Yazi D
YD
Hodges
John R
JR
Xuereb
John H
JH
Gregory
Gillian C
GC
Halliday
Glenda M
GM
Götz
Jürgen
J
Kril
Jillian J
JJ
Ittner
Lars M
LM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010766:Phosphorylation; D020774:Pick Disease of the Brain / Q000201:enzymology / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
C054369:MAPT protein, human; D016875:tau Proteins; D048056:Mitogen-Activated Protein Kinase 9; D000071679:Glycogen Synthase Kinase 3 beta; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D038362:Glycogen Synthase Kinase 3
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