Seeding of A beta fibril formation is inhibited by all three isotypes of apolipoprotein E - PubMed (original) (raw)
. 1996 Sep 24;35(38):12623-8.
doi: 10.1021/bi961074j.
Affiliations
- PMID: 8823200
- DOI: 10.1021/bi961074j
Seeding of A beta fibril formation is inhibited by all three isotypes of apolipoprotein E
S J Wood et al. Biochemistry. 1996.
Abstract
Apolipoprotein E is immunochemically localized to amyloid plaque in Alzheimer's brains, and the allelic distribution of ApoE in individuals is associated with a disposition toward Alzheimer's disease. We show here that all three ApoE isotypes exhibit a strong and specific ability to inhibit both nucleation and seeding of fibril formation by the A beta peptide in vitro. A beta (1-40) depleted of aggregates requires long incubation times before the onset of fibril formation, but addition of very low levels of A beta fibrils to such reactions is sufficient to reduce or eliminate this lag time. ApoE added to such seeded reactions extends the lag time in a dose-dependent manner, so that higher levels of seeding require higher levels of ApoE to achieve a given delay time to reaction onset. This effect is observed with all three isotypes produced in Escherichia coli, as well as with plasma-derived ApoE and the N-terminal domain of ApoE3 produced in E. coli. In contrast, bovine serum albumin and the four-helix bundle protein interleukin-4 are poor inhibitors of seeding. ApoE3 can also inhibit fibril formation by A beta (1-42). The three full-length isotypes of ApoE produced in E. coli are equipotent at inhibition. It is therefore possible that the genetics of ApoE and AD may fundamentally depend on the ability of ApoE to inhibit seeding but that the trends in the genetics must be related to something other than the specific activities of the native ApoE isoforms used in these studies. The data show ApoE to be the first member of a new class of fibril formation inhibitor that acts by blocking the seeding of fibril growth.
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 - Association of human, rat, and rabbit apolipoprotein E with beta-amyloid.
LaDu MJ, Lukens JR, Reardon CA, Getz GS. LaDu MJ, et al. J Neurosci Res. 1997 Jul 1;49(1):9-18. J Neurosci Res. 1997. PMID: 9211985 - 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. - Isoform-specific interactions of human apolipoprotein E to an intermediate conformation of human Alzheimer amyloid-beta peptide.
Stratman NC, Castle CK, Taylor BM, Epps DE, Melchior GW, Carter DB. Stratman NC, et al. Chem Phys Lipids. 2005 Oct;137(1-2):52-61. doi: 10.1016/j.chemphyslip.2005.06.005. Chem Phys Lipids. 2005. PMID: 16140289 - ApoE: crossroads between Alzheimer's disease and atherosclerosis.
Stojakovic T, Scharnagl H, März W. Stojakovic T, et al. Semin Vasc Med. 2004 Aug;4(3):279-85. doi: 10.1055/s-2004-861496. Semin Vasc Med. 2004. PMID: 15630629 Review.
Cited by
- Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease.
Holtzman DM, Herz J, Bu G. Holtzman DM, et al. Cold Spring Harb Perspect Med. 2012 Mar;2(3):a006312. doi: 10.1101/cshperspect.a006312. Cold Spring Harb Perspect Med. 2012. PMID: 22393530 Free PMC article. Review. - The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review.
Nixon RA, Cataldo AM, Mathews PM. Nixon RA, et al. Neurochem Res. 2000 Oct;25(9-10):1161-72. doi: 10.1023/a:1007675508413. Neurochem Res. 2000. PMID: 11059790 Review. - Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy.
Endo Y, Hasegawa K, Nomura R, Arishima H, Kikuta KI, Yamashita T, Inoue Y, Ueda M, Ando Y, Wilson MR, Hamano T, Nakamoto Y, Naiki H. Endo Y, et al. Acta Neuropathol Commun. 2019 Jan 28;7(1):12. doi: 10.1186/s40478-019-0662-1. Acta Neuropathol Commun. 2019. PMID: 30691533 Free PMC article. - The Important Interface Between Apolipoprotein E and Neuroinflammation in Alzheimer's Disease.
Kloske CM, Wilcock DM. Kloske CM, et al. Front Immunol. 2020 Apr 30;11:754. doi: 10.3389/fimmu.2020.00754. eCollection 2020. Front Immunol. 2020. PMID: 32425941 Free PMC article. Review. - Targeting the accomplice to thwart the culprit: a new target for the prevention of amyloid deposition.
Borchelt DR. Borchelt DR. J Clin Invest. 2018 May 1;128(5):1734-1736. doi: 10.1172/JCI120414. Epub 2018 Mar 30. J Clin Invest. 2018. PMID: 29600962 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous