Alzheimer's disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular
senile plaques. Although there have been numerous studies on
tau proteins and AD in various stages of
neurodegenerative disease pathology, the relationship between tau and AD is not yet fully understood. A transgenic mouse model expressing
neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain
proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex
proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified
proteins,
glutathione S-transferase P 1 (GSTP1) and
carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type
proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The
proteins, which were further confirmed by RT-PCR at the
mRNA level and with western blotting at the
protein level, are expected to be good candidates as
drug targets for AD. The study of up- and down-regulation of
proteins during the progression of AD helps to explain the mechanisms associated with neuronal degeneration in AD.