Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides - PubMed (original) (raw)
. 2000 Jun 1;348 Pt 2(Pt 2):359-65.
M Calero, E Matsubara, R Vidal, A Kumar, B Permanne, B Zlokovic, J D Smith, M J Ladu, A Rostagno, B Frangione, J Ghiso
Affiliations
- PMID: 10816430
- PMCID: PMC1221074
Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides
T Tokuda et al. Biochem J. 2000.
Abstract
The inheritance of the apolipoprotein E (apoE) epsilon4 allele is a prevailing risk factor for sporadic and familial Alzheimer's disease (AD). ApoE isoforms bind directly to Alzheimer's amyloid beta (Abeta) peptides both in vitro and in vivo. Recent studies suggest that association of apoE with lipids may modulate its interaction with Abeta. We examined the binding of lipid-associated and delipidated apoE3 and apoE4 isoforms to Abeta utilizing a solid-phase binding assay and estimated the dissociation constants for the interaction of various apoE and Abeta species. Using native apoE isoforms from stably transfected RAW 264 and human embryonic kidney 293 cells, apoE3 had greater affinity than apoE4 for both Abeta1-40 and Abeta1-42. Delipidation of apoE decreased its affinity for Abeta peptides by 5-10-fold and abolished the isoform-specificity. Conversely, incorporation of apoE isoforms produced by baculovirus-infected Sf9 cells into reconstituted human high-density-lipoprotein lipoparticles restored the affinity values for Abeta peptides and resulted in preferential binding of apoE3. The data demonstrate that native lipid-associated apoE3 binds to Abeta peptides with 2-3-fold higher affinity than lipid-associated apoE4. Since the isoforms' binding efficiency correlate inversely with the risk of developing late-onset AD, the results suggest a possible involvement of apoE3 in the clearance or routing out of Abeta from the central nervous system as one of the mechanisms underlying the pathology of the disease.
Similar articles
- Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1-40). Relevance to Alzheimer's disease.
Aleshkov S, Abraham CR, Zannis VI. Aleshkov S, et al. Biochemistry. 1997 Aug 26;36(34):10571-80. doi: 10.1021/bi9626362. Biochemistry. 1997. PMID: 9265639 - Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 isoforms and to isoforms from human plasma.
Yang DS, Smith JD, Zhou Z, Gandy SE, Martins RN. Yang DS, et al. J Neurochem. 1997 Feb;68(2):721-5. doi: 10.1046/j.1471-4159.1997.68020721.x. J Neurochem. 1997. PMID: 9003062 - ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA.
Yajima R, Tokutake T, Koyama A, Kasuga K, Tezuka T, Nishizawa M, Ikeuchi T. Yajima R, et al. Biochem Biophys Res Commun. 2015 Jan 2;456(1):482-8. doi: 10.1016/j.bbrc.2014.11.111. Epub 2014 Dec 5. Biochem Biophys Res Commun. 2015. PMID: 25482438 - The interaction of amyloid-beta with ApoE.
Carter DB. Carter DB. Subcell Biochem. 2005;38:255-72. doi: 10.1007/0-387-23226-5_13. Subcell Biochem. 2005. PMID: 15709483 Review. - Apolipoprotein E isoforms in Alzheimer's disease pathology and etiology.
Baum L, Chen L, Ng HK, Pang CP. Baum L, et al. Microsc Res Tech. 2000 Aug 15;50(4):278-81. doi: 10.1002/1097-0029(20000815)50:4<278::AID-JEMT5>3.0.CO;2-T. Microsc Res Tech. 2000. PMID: 10936880 Review.
Cited by
- Discovery of Small Molecule Glycolytic Stimulants for Enhanced ApoE Lipidation in Alzheimer's Disease Cell Model.
Patil SP, Kuehn BR. Patil SP, et al. Pharmaceuticals (Basel). 2024 Apr 12;17(4):491. doi: 10.3390/ph17040491. Pharmaceuticals (Basel). 2024. PMID: 38675451 Free PMC article. - Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.
Huang Z. Huang Z. J Alzheimers Dis. 2024;99(2):447-470. doi: 10.3233/JAD-240042. J Alzheimers Dis. 2024. PMID: 38669548 Free PMC article. Review. - The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer's Disease.
Lozupone M, Dibello V, Sardone R, Castellana F, Zupo R, Lampignano L, Bortone I, Daniele A, Bellomo A, Solfrizzi V, Panza F. Lozupone M, et al. Biology (Basel). 2023 Dec 15;12(12):1529. doi: 10.3390/biology12121529. Biology (Basel). 2023. PMID: 38132357 Free PMC article. Review. - An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele.
Meuret CJ, Hu Y, Smadi S, Bantugan MA, Xian H, Martinez AE, Krauss RM, Ma QL, Nedelkov D, Yassine HN. Meuret CJ, et al. Alzheimers Res Ther. 2023 May 23;15(1):96. doi: 10.1186/s13195-023-01239-0. Alzheimers Res Ther. 2023. PMID: 37221560 Free PMC article. - Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.
Valencia-Olvera AC, Balu D, Faulk N, Amiridis A, Wang Y, Pham C, Avila-Munoz E, York JM, Thatcher GRJ, LaDu MJ. Valencia-Olvera AC, et al. Neurotherapeutics. 2023 Jul;20(4):1120-1137. doi: 10.1007/s13311-023-01375-3. Epub 2023 May 8. Neurotherapeutics. 2023. PMID: 37157042 Free PMC article.
References
- Biochim Biophys Acta. 1990 Oct 22;1047(1):99-101 - PubMed
- Brain Res. 1991 Feb 8;541(1):163-6 - PubMed
- Brain Res Mol Brain Res. 1991 Sep;11(2):97-106 - PubMed
- Neurosci Lett. 1992 Feb 3;135(2):235-8 - PubMed
- Nature. 1992 Sep 24;359(6393):325-7 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous