+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration



Phosphorylated map kinase (ERK1, ERK2) expression is associated with early tau deposition in neurones and glial cells, but not with increased nuclear DNA vulnerability and cell death, in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration



Brain Pathology 11(2): 144-158



Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in taupathies. The present study examines the involvement of the Ras/MEK/ERK pathway of tau phosphorylation in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), by Western blotting, single and double-labelling immunohistochemistry, and p21Ras activation assay. Since this pathway is also activated in several paradigms of cell death and cell survival, activated ERK expression is also analysed with double-labelling immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation to visualise activated ERK in cells with increased nuclear DNA vulnerability. The MEK1 antibody recognises one band of 45 kD that identifies phosphorylation-independent MEK1, whose expression levels are not modified in diseased brains. The ERK antibody recognises one band of 42 kD corresponding to the molecular weight of phosphorylation-independent ERK2; the expression levels, as well as the immunoreactivity of ERK in individual cells, is not changed in AD, PiD, PSP and CBD. The antibody MAPK-P distinguishes two bands of 44 kD and 42 kD that detect phosphorylated ERK1 and ERK2. MAPK-P expression levels, as seen with Western blotting, are markedly increased in AD, PiD, PSP and CBD. Moreover, immunohistochemistry discloses granular precipitates in the cytoplasm of neurones in AD, mainly in a subpopulation of neurones exhibiting early tau deposition, whereas neurones with developed neurofibrillary tangles are less commonly immunostained. MAPK-P also decorates neurones with Pick bodies in PiD, early tau deposition in neurones in PSP and CBD, and cortical achromatic neurones in CBD. In addition, strong MAPK-P immunoreactivity is found in large numbers of tau-positive glial cells in PSP and CBD, as seen with double-labelling immunohistochemistry. Yet no co-localisation of enhanced phosphorylated ERK immunoreactivity and nuclear DNA fragmentation is found in AD, PiD, PSP and CBD. Finally, activated Ras expression levels are increased in AD cases when compared with controls. These results demonstrate increased phosphorylated (active) ERK expression in association with early tau deposition in neurones and glial cells in taupathies, and suggest activated Ras as the upstream activator of the MEK/ERK pathway of tau phosphorylation in AD.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011144481

Download citation: RISBibTeXText

PMID: 11303790

DOI: 10.1111/j.1750-3639.2001.tb00387.x


Related references

Phosphorylated c-Myc expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Neuropathology and Applied Neurobiology 27(5): 343-351, 2001

Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathologica 104(6): 583-591, 2002

Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathologica 101(2): 167-173, 2001

Tau-positive glial inclusions in progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Brain Pathology 9(4): 663-679, 1999

Different immunoreactivities of the microtubule-binding region of tau and its molecular basis in brains from patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathologica 105(5): 489-498, 2003

Similarities and differences among progressive among progressive supranuclear palsy, corticobasal degeneration and Pick's disease. Neuropathology 16(4): 262-268, 1996

Neuropathologic overlap of progressive supranuclear palsy, Pick's disease and corticobasal degeneration. Journal of Neuropathology and Experimental Neurology 55(1): 53-67, 1996

Phosphorylated Smad 2/3 colocalizes with phospho-tau inclusions in Pick disease, progressive supranuclear palsy, and corticobasal degeneration but not with alpha-synuclein inclusions in multiple system atrophy or dementia with Lewy bodies. Journal of Neuropathology and Experimental Neurology 66(11): 1019-1026, 2007

Tau-positive dial Inclusions in Progressive Supranuclear Palsy, Corticobasal Degeneration and Pick's Disease. Brain Pathology 9(4): 663-679, 1999

Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick's disease. Brain Pathology 9(4): 681-693, 1999

The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer's disease. Neurology 45(8): 1477-1483, 1995

Abnormal cytoskeletal pathology peculiar to corticobasal degeneration is different from that of Alzheimer's disease or progressive supranuclear palsy. Acta Neuropathologica 88(4): 379-383, 1994

Basal ganglia lesions in corticobasal degeneration differ from those in Pick's disease and progressive supranuclear palsy: A topographic neuropathological study of six autopsy cases. Neuropathology 17(3): 208-216, 1997

Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX. Acta Neuropathologica Communications 4(1): 118, 2016

Morphologic difference of neuropil threads in Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy: A morphometric study. Neuroscience Letters 233(2-3): 89-92, 1997