Premium
Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles
Author(s) -
Tandon Anurag,
Yu Haung,
Wang Linda,
Rogaeva Ekaterina,
Sato Christine,
Chishti M. Azhar,
Kawarai Toshitaka,
Hasegawa Hiroshi,
Chen Fusheng,
Davies Peter,
Fraser Paul E.,
Westaway David,
St GeorgeHyslop Peter H.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01865.x
Subject(s) - progressive supranuclear palsy , frontotemporal dementia , tauopathy , corticobasal degeneration , neuroscience , alzheimer's disease , cyclin dependent kinase 5 , neurofibrillary tangle , proteolysis , frontotemporal lobar degeneration , dementia , neurodegeneration , pathology , chemistry , psychology , biology , disease , medicine , senile plaques , biochemistry , kinase , enzyme , mitogen activated protein kinase kinase , protein kinase a
Abstract Elevated levels of p25 and constitutive activation of CDK5 have been observed in AD brains. This has led to the hypothesis that increased p25 levels could promote neurofibrillary tangles (NFT) through CDK5‐mediated hyperphosphorylation of tau, the principal component of NFTs. We examined p25 immunoreactivity in brains from sporadic and familial AD cases, as well as other neurologic diseases that exhibit NFT, such as Down's syndrome (DS), Pick's disease (Pick), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD). Neither the p25 immunoreactivity nor the p25/p35 ratio was elevated in the AD brains or in the other tauopathies ( n = 34) compared with controls ( n = 11). Although Aβ peptides have been suggested to activate calpain‐mediated cleavage of p35 to p25 in cultured neurons, p25 levels in brains of TgCRND8 mice, which express high levels of brain Aβ peptides, were similar to those of non‐Tg littermates. Our data suggest that high Aβ levels in brain do not activate p35 proteolysis, and p25 is unlikely to be a causative agent for NFT formation in AD or other tauopathies.