2026-04-17T11:54:15Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1907852025-12-04T19:02:30Zcom_2072_1057col_2072_478777col_2072_478917

Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients. Lennol, Matthew Paul Sánchez-Domínguez, Irene Cuchillo-Ibañez, Inmaculada Camporesi, Elena Brinkmalm, Gunnar Alcolea, Daniel Fortea, Juan Lleó Bisa, Alberto Soria, Guadalupe Aguado Tomàs, Fernando Zetterberg, Henrik Blennow, Kaj Sáez-Valero, Javier Malaltia d'Alzheimer Líquid cefalorraquidi Alzheimer's disease Cerebrospinal fluid 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. 2022-11-14T14:34:45Z 2022-11-14T14:34:45Z 2022-11-02 2022-11-14T14:34:45Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1758-9193 https://hdl.handle.net/2445/190785 726535 eng Reproducció del document publicat a: https://doi.org/10.1186/s13195-022-01108-2 Alzheimers Research & Therapy, 2022, vol. 14, num. 161, p. 1-19 https://doi.org/10.1186/s13195-022-01108-2 info:eu-repo/grantAgreement/EC/H2020/681712/EU//PATHAD info:eu-repo/grantAgreement/EC/H2020/860197/EU//860197 cc-by (c) Lennol, Matthew Paul et al., 2022 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess 19 p. application/pdf BioMed Central Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)