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Cited by 239Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Ferrer, I., Blanco, R., Carmona, M., Ribera, R., Goutan, E., Puig, B., Rey, M.J., Cardozo, A. +2 more·2001·Brain Pathology
DOI 10.1111/j.1750-3639.2001.tb00387.xPMC PMC8098611
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Abstract

Abnormal tau phosphorylation and deposition in neurones and glial cells is one of the major features in tau pathies. 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.

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Authors
Ferrer, I., Blanco, R., Carmona, M., Ribera, R., Goutan, E., Puig, B., Rey, M. J., Cardozo, A., Viñals, F., & Ribalta, T.
Affiliations
  • Hospital Clínic de Barcelona (ES)
  • Universitat de Barcelona (ES)
Corresponding author
Ferrer, I.
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2001-04
Volume
11
Issue
2
Pages
144-158
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2001.tb00387.x
PMC
PMC8098611
OpenAlex
W2054223500
Cited by
239
References
5
Citations by year
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FWCI
12.98
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1830 d)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau phosphorylation, ERK1/2, MEK1, Ras/MEK/ERK pathway, tauopathy, Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, tau deposition, Pick bodies, neurofibrillary tangles, glial cells, neuronal cell death, nuclear DNA fragmentation, Ras activation, mitogen-activated protein kinase
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Basal Ganglia Diseases, Cell Nucleus, Cerebral Cortex, DNA, Female, Humans, Male, Middle Aged, Nerve Degeneration, Neuroglia, Neurons, Phosphorylation, Supranuclear Palsy, Progressive, Proto-Oncogene Proteins p21(ras), tau Proteins, Cell Death, Mitogen-Activated Protein Kinase 1, Pick Disease of the Brain, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, DNA Fragmentation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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