Oligodendrocytes are a Novel Source of Amyloid Peptide Generation

Skaper, Stephen D.; Evans, Nicholas A.; Soden, Peter E.; Rosin, Claudia; Facci, Laura; Richardson, Jill C.

doi:10.1007/s11064-009-0022-9

Cited by 43Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Oligodendrocytes are a Novel Source of Amyloid Peptide Generation

Skaper, Stephen D., Evans, Nicholas A., Soden, Peter E., Rosin, Claudia, Facci, Laura, Richardson, Jill C.·2009·Neurochemical Research

DOI 10.1007/s11064-009-0022-9

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Abstract

Alzheimer’s disease is characterised by regional neuronal degeneration, synaptic loss, and the progressive deposition of the 4 kDa β-amyloid peptide (Aβ) in senile plaques and accumulation of tau protein as neurofibrillary tangles. Aβ derives from the larger precursor molecule, amyloid precursor protein (APP) by proteolytic processing via β- and γ-secretases. While APP expression is well documented in neurons and astrocytes, the case for oligodendrocytes is less clear. The latter cell type is reported to express different isoforms of APP, and we have confirmed this observation by immunocytochemistry in cultures of differentiated rat cortical oligodendrocytes. Moreover, by means of a sensitive electrochemiluminescent immunoassay employing Aβ C-terminal specific antibodies, mature oligodendrocytes are shown to secrete the 40 and 42 amino acid Aβ species (Aβ40 and Aβ42). Secretion of Aβ peptides was reduced by incubating oligodendrocytes with α- and β-secretase inhibitors, or a γ-secretase inhibitor. Disturbances of APP processing and/ or synthesis in oligodendrocytes may account for some myelin disorders observed in Alzheimer's disease and other senile dementias.

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“Cultured oligodendrocytes (OLs) are capable of generating detectable levels of Aβ in vitro4–6.”
From Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice (2024) · cites this paper as [4]

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Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease
Chiarini, A., Armato, U., Liu, D., & Dal Prà, I. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00134 · Cited by 51 · see citing works

β-Amyloid Protein is Higher in Alzheimerʼs Disease Brains
Frucht, S. J., & Koo, E. H. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199311000-00011 · Cited by 15 · see citing works
Phosphorylation of Amyloid Precursor Protein (APP) Family Proteins
Suzuki, T., Ando, K., Iijima, K., Oguchi, S., & Takeda, S. (2003) · Humana Press eBooks · doi:10.1385/1-59259-195-7:271 · Cited by 3 · see citing works
Processing of Amyloid Precursor Protein and Amyloid Peptide Neurotoxicity
Pierrot, N., & Jean-Noël, O. (2008) · Current Alzheimer Research · doi:10.2174/156720508783954721 · Cited by 60 · see citing works
Antisera to an amino-terminal peptide detect the amyloid protein precursor of alzheimer's disease and recognize senile plaques
Palmert, M. R., Podlisny, M. B., Witker, D. S., Oltersdorf, T., Younkin, L. H., Selkoe, D. J., & Younkin, S. G. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80859-3 · Cited by 81 · see citing works
Avid Binding of βA Amyloid Peptide to Its Own Precursor
Strittmatter, W. J., Huang, D. Y., Bhasin, R., Roses, A. D., & Goldgaber, D. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1132 · Cited by 28 · see citing works

Authors: Skaper, S. D., Evans, N. A., Soden, P. E., Rosin, C., Facci, L., & Richardson, J. C.
Affiliations: University of Padua (IT)
GlaxoSmithKline (United Kingdom) (GB)
Corresponding author: Skaper, Stephen D.
ORCID: Skaper, Stephen D.
Soden, Peter E.
Richardson, Jill C.
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2009-06-26
Volume: 34
Issue: 12
Pages: 2243-2250
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-009-0022-9
OpenAlex: W2021746799
Cited by: 43
References: 73
Citations by year: 2026: 2 · 2025: 5 · 2024: 6 · 2023: 8 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 1
FWCI: 0.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neurochemical Research (publishedVersion)
PubMed (publishedVersion)
Funders: Biotechnology and Biological Sciences Research Council (01/A4/C/07710)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: oligodendrocytes, amyloid-beta, Alzheimer's disease, amyloid precursor protein, APP isoforms, APP processing, secretase inhibitors, gamma-secretase, myelin disorders, amyloid plaques, neurofibrillary tangles
MeSH terms: Alzheimer Disease, Animals, Oligodendroglia, Peptide Fragments, Thiazines, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Amyloid Precursor Protein Secretases

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Oligodendrocytes are a Novel Source of Amyloid Peptide Generation

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