Cited by 281Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

PP2A mRNA Expression Is Quantitatively Decreased in Alzheimer's Disease Hippocampus

Vogelsberg-Ragaglia, Vanessa, Schuck, Theresa, Trojanowski, John Q, Lee, Virginia M.-Y·2001·Experimental Neurology

Abstract

Since abnormal tau phosphorylation may play a role in neurofibrillary tangle (NFT) formation in aging and Alzheimer's disease (AD), we probed the distribution and abundance of protein phosphatase 2A (PP2A) catalytic (Calpha) and regulatory (PR55alpha and gamma, PR61varepsilon and delta) subunit mRNA in control and AD hippocampus using in situ hybridization. Quantitation of grain density per neuron area of PP2A subunits and beta-actin was determined for the CA3 region of hippocampus and cerebellum, while a qualitative assessment was performed for CA1, CA4, and dentate gyrus. All subunits are expressed in neurons, while PR55gamma and PR55alpha mRNA are also evident in glia. The expression levels of Calpha, all PP2A regulatory subunits studied, and beta-actin were similar in control and AD cerebellum. beta-Actin mRNA was, however, reduced in AD hippocampus. In addition to the generalized reduction of mRNA, as indicated by decreased beta-actin signal, there was a significant loss of Calpha, PR55gamma, and PR61epsilon mRNA in the CA3 hippocampus of AD. This study delineates the distribution of critical PP2A mRNAs and reveals a neuron- and subunit-specific reduction in PP2A catalytic and regulatory mRNA in AD hippocampus. This could result in decreased protein expression and phosphatase activity, leading to the hyperphosphorylation of tau and the formation of NFTs, as well as neuron degeneration in AD.

Integrity signals

Registry

Crossref · 10.1006/exnr.2001.7630

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63 of 63 references verified0 citation errors · 0 not checkable

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  • Increased GSK3β expression and CDK5 activity, decreased expression of PP1 and PP2A, and decreased PP2A activity have been observed in specific brain regions in AD patients.

    “In support of this, increased GSK3β expression and CDK5 activity, decreased expression of PP1 and PP2A, and decreased PP2A activity has been observed in specific brain regions in AD patients [148–152].”

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Authors
Vogelsberg-Ragaglia, V., Schuck, T., Trojanowski, J. Q., & Lee, V. M.-Y.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lee, Virginia M.-Y
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2001-04
Volume
168
Issue
2
Pages
402-412
ISSN
0014-4886 (ISSN-L)
OpenAlex
W2169217121
Cited by
281
References
63
Citations by year
2026: 7 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 12 · 2019: 4 · 2018: 7 · 2017: 16 · 2016: 9 · 2015: 6 · 2014: 13 · 2013: 12 · 2012: 16
FWCI
5.89
Type
journal article
Language
en
Open access
closed
Locations
  • Experimental Neurology (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
Alzheimer's disease, protein phosphatase 2A, PP2A catalytic subunit, PP2A regulatory subunit, tau hyperphosphorylation, neurofibrillary tangles, hippocampus, CA3, mRNA expression, beta-actin, cerebellum, neuron-specific gene expression, glial expression
MeSH terms
Actins, Aged, Aged, 80 and over, Alzheimer Disease, Cerebellum, Female, Hippocampus, Humans, Male, Neuroglia, Neurons, Phosphoprotein Phosphatases, RNA, Messenger, Protein Phosphatase 2

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