Decreased brain levels of 2′,3′-cyclic nucleotide-3′-phosphodiesterase in Down syndrome and Alzheimer’s disease
Abstract
In Down syndrome (DS) as well as in Alzheimer's disease (AD) oligodendroglial and myelin alterations have been reported. 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) and carbonic anhydrase II (CA II) are widely accepted as markers for oligodendroglia and myelin. However, only data on CNPase activity have been available in AD and DS brains so far. In our study we determined the protein levels of CNPase and CA II in DS, AD and in control post mortem brain samples in order to assess oligodendroglia and myelin alterations in both diseases. We used two dimensional electrophoresis to separate brain proteins that were subsequently identified by matrix assisted laser desorption and ionization mass-spectroscopy (MALDI-MS). Seven brain areas were investigated (frontal, temporal, occipital and parietal cortex, cerebellum, thalamus and caudate nucleus). In comparison to control brains we detected significantly decreased CNPase protein levels in frontal and temporal cortex of DS patients. The level of CA II protein in DS was unchanged in comparison to controls. In AD brains levels of CNPase were decreased in frontal cortex only. The level of CA II in all brain areas in AD group was comparable to controls. Changes of CNPase protein levels in DS and AD are in agreement with the previous finding of decreased CNPase activity in DS and AD brain. They probably reflect decreased oligodendroglial density and/or reduced myelination. These can be secondary to disturbances in axon/oligodend…
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AD pathology in the white matter includes loss of myelin and a decrease in oligodendrocyte proteins.
“AD pathology in the white matter includes the loss of myelin and a decrease in oligodendrocyte proteins [62–68].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [62]
Lower levels of 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNP), an oligodendrocyte specific protein, have been detected in the front and temporal lobes of tissue samples from Down syndrome versus controls.
“In addition, lower levels of 2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNP), an OL specific protein, have also been detected in the front and temporal lobes of tissue samples from DS versus controls (Vlkolinský et al., 2001).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Vlkolinský et al., 2001
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Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease
Bartzokis, G. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.03.001 · Cited by 968 · see citing works
White matter changes in Alzheimer’s disease: A focus on myelin and oligodendrocytes
Nasrabady, S. E., Rizvi, B., Goldman, J. E., & Brickman, A. M. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0515-3 · Cited by 723 · see citing works
Alzheimer's disease as homeostatic responses to age-related myelin breakdown
Bartzokis, G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.007 · Cited by 546 · see citing works
Behrendt, G., Baer, K., Buffo, A., Curtis, M. A., Faull, R. L., Rees, M. I., Götz, M., & Dimou, L. (2013) · Glia · doi:10.1002/glia.22432 · Cited by 219 · see citing works
De Rossi, P., Buggia-Prévot, V., Clayton, B. L. L., Vasquez, J. B., van Sanford, C., Andrew, R. J., Lesnick, R., Botté, A., Deyts, C., Salem, S., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0124-1 · Cited by 151 · see citing works
“AD pathology in the white matter includes the loss of myelin and a decrease in oligodendrocyte proteins [62 – 68].”
Sultana, R., Perluigi, M., Newman, S. F., Pierce, W. M., Cini, C., Coccia, R., & Butterfield, D. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2810 · Cited by 125 · see citing works
Wu, D., Tang, X., Gu, L., Li, X., Qi, X., Bai, F., Chen, X., Wang, J., Ren, Q., & Zhang, Z. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12809 · Cited by 64 · see citing works
Neurodevelopment in Down syndrome: Concordance in humans and models
Klein, J. A., & Haydar, T. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.941855 · Cited by 47 · see citing works
“In addition, lower levels of 2,3-cyclic nucleotide-3-phosphodiesterase (CNP), an OL specific protein, have also been detected in the front and temporal lobes of tissue samples from DS versus controls (Vlkolinský et al., 2001).”
Background
- Authors
- Vlkolinský, R., Cairns, N., Fountoulakis, M., & Lubec, G.
- Affiliations
- University of Vienna (AT)
- King's College London (GB)
- F. Hoffmann-La Roche AG (CH)
- ORCID
- Vlkolinský, Roman
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 22
- Issue
- 4
- Pages
- 547-553
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2058622897
- Cited by
- 95
- References
- 1
- Citations by year
- 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 8 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 5 · 2012: 4
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- CNPase, carbonic anhydrase II, Down syndrome, Alzheimer's disease, oligodendroglia, myelination, frontal cortex, temporal cortex, postmortem brain
- MeSH terms
- Aged, Alzheimer Disease, Brain, Carbonic Anhydrases, Down Syndrome, Female, Humans, Male, Middle Aged, Nerve Degeneration, Oligodendroglia, 2',3'-Cyclic-Nucleotide Phosphodiesterases, Electrophoresis, Gel, Two-Dimensional, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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