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http://hdl.handle.net/2445/190785
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DC Field | Value | Language |
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dc.contributor.author | Lennol, Matthew Paul | - |
dc.contributor.author | Sánchez-Domínguez, Irene | - |
dc.contributor.author | Cuchillo-Ibañez, Inmaculada | - |
dc.contributor.author | Camporesi, Elena | - |
dc.contributor.author | Brinkmalm, Gunnar | - |
dc.contributor.author | Alcolea, Daniel | - |
dc.contributor.author | Fortea, Juan | - |
dc.contributor.author | Lleó Bisa, Alberto | - |
dc.contributor.author | Soria, Guadalupe | - |
dc.contributor.author | Aguado Tomàs, Fernando | - |
dc.contributor.author | Zetterberg, Henrik | - |
dc.contributor.author | Blennow, Kaj | - |
dc.contributor.author | Sáez-Valero, Javier | - |
dc.date.accessioned | 2022-11-14T14:34:45Z | - |
dc.date.available | 2022-11-14T14:34:45Z | - |
dc.date.issued | 2022-11-02 | - |
dc.identifier.issn | 1758-9193 | - |
dc.identifier.uri | http://hdl.handle.net/2445/190785 | - |
dc.description.abstract | Objective: The purpose of this study was to examine the levels of cerebrospinal fluid (CSF) apolipoprotein E (apoE) species in Alzheimer's disease (AD) patients. Methods: We analyzed two CSF cohorts of AD and control individuals expressing different APOE genotypes. Moreover, CSF samples from the TgF344-AD rat model were included. Samples were run in native- and SDS-PAGE under reducing or non-reducing conditions (with or without β-mercaptoethanol). Immunoprecipitation combined with mass spectrometry or western blotting analyses served to assess the identity of apoE complexes. Results: In TgF344-AD rats expressing a unique apoE variant resembling human apoE4, a ~35-kDa apoE monomer was identified, increasing at 16.5 months compared with wild-types. In humans, apoE isoforms form disulfide-linked dimers in CSF, except apoE4, which lacks a cysteine residue. Thus, controls showed a decrease in the apoE dimer/monomer quotient in the APOE ε3/ε4 group compared with ε3/ε3 by native electrophoresis. A major contribution of dimers was found in APOE ε3/ε4 AD cases, and, unexpectedly, dimers were also found in ε4/ε4 AD cases. Under reducing conditions, two apoE monomeric glycoforms at 36 kDa and at 34 kDa were found in all human samples. In AD patients, the amount of the 34-kDa species increased, while the 36-kDa/34-kDa quotient was lower compared with controls. Interestingly, under reducing conditions, a ~100-kDa apoE complex, the identity of which was confirmed by mass spectrometry, also appeared in human AD individuals across all APOE genotypes, suggesting the occurrence of aberrantly resistant apoE aggregates. A second independent cohort of CSF samples validated these results. Conclusion: These results indicate that despite the increase in total apoE content the apoE protein is altered in AD CSF, suggesting that function may be compromised. | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s13195-022-01108-2 | - |
dc.relation.ispartof | Alzheimers Research & Therapy, 2022, vol. 14, num. 161, p. 1-19 | - |
dc.relation.uri | https://doi.org/10.1186/s13195-022-01108-2 | - |
dc.rights | cc-by (c) Lennol, Matthew Paul et al., 2022 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) | - |
dc.subject.classification | Malaltia d'Alzheimer | - |
dc.subject.classification | Líquid cefalorraquidi | - |
dc.subject.other | Alzheimer's disease | - |
dc.subject.other | Cerebrospinal fluid | - |
dc.title | Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients. | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 726535 | - |
dc.date.updated | 2022-11-14T14:34:45Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/681712/EU//PATHAD | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/860197/EU//860197 | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
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