PP2A mRNA Expression Is Quantitatively Decreased in Alzheimer's Disease Hippocampus
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.
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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].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [150]
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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
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- 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
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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