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Cited by 38Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The ability of apolipoprotein E fragments to promote intraneuronal accumulation of amyloid beta peptide 42 is both isoform and size-specific

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Dafnis, Ioannis, Argyri, Letta, Sagnou, Marina, Tzinia, Athina, Tsilibary, Effie C., Stratikos, Efstratios, Chroni, Angeliki·2016·Scientific Reports
DOI 10.1038/srep30654PMC PMC4967930
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Abstract

The apolipoprotein (apo) E4 isoform is the strongest risk factor for late-onset Alzheimer’s disease (AD). ApoE4 is more susceptible to proteolysis than apoE2 and apoE3 isoforms and carboxyl-terminal truncated apoE4 forms have been found in AD patients’ brain. We have previously shown that a specific apoE4 fragment, apoE4-165, promotes amyloid-peptide beta 42 (Aβ42) accumulation in human neuroblastoma SK-N-SH cells and increased intracellular reactive oxygen species formation, two events considered to occur early in AD pathogenesis. Here, we show that these effects are allele-dependent and absolutely require the apoE4 background. Furthermore, the exact length of the fragment is critical since longer or shorter length carboxyl-terminal truncated apoE4 forms do not elicit the same effects. Structural and thermodynamic analyses showed that apoE4-165 has a compact structure, in contrast to other carboxyl-terminal truncated apoE4 forms that are instead destabilized. Compared however to other allelic backgrounds, apoE4-165 is structurally distinct and less thermodynamically stable suggesting that the combination of a well-folded structure with structural plasticity is a unique characteristic of this fragment. Overall, our findings suggest that the ability of apoE fragments to promote Aβ42 intraneuronal accumulation is specific for both the apoE4 isoform and the particular structural and thermodynamic properties of the fragment.

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Cited by

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Authors
Dafnis, I., Argyri, L., Sagnou, M., Tzinia, A., Tsilibary, E. C., Stratikos, E., & Chroni, A.
Affiliations
National Centre of Scientific Research "Demokritos" (GR)
Corresponding author
Chroni, Angeliki
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-08-01
Volume
6
Issue
1
Pages
30654-30654
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep30654
PMC
PMC4967930
OpenAlex
W2495903187
Cited by
38
References
11
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 9 · 2018: 6 · 2017: 4
FWCI
5.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • European Commission
  • European Social Fund
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
APOE ε4, amyloid-beta 42, Alzheimer's disease, protein folding stability, thermodynamic stability, reactive oxygen species, SK-N-SH cells
MeSH terms
Apolipoproteins E, Humans, Neurons, Peptide Fragments, Protein Conformation, Tumor Cells, Cultured, Amyloid beta-Peptides, Protein Folding, Protein Isoforms, Apolipoprotein E4, Protein Stability

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