Fibrillogenesis in Alzheimer's disease of amyloid beta peptides and apolipoprotein E - PubMed (original) (raw)

Fibrillogenesis in Alzheimer's disease of amyloid beta peptides and apolipoprotein E

E M Castano et al. Biochem J. 1995.

Abstract

A central event in Alzheimer's disease is the conformational change from normally circulating soluble amyloid beta peptides (A beta) and tau proteins into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively. The apolipoprotein E (apoE) gene locus has recently been associated with late-onset Alzheimer's disease. It is not know whether apoE plays a direct role in the pathogenesis of the disease. In the present work we have investigated whether apoE can affect the known spontaneous in vitro formation of amyloid-like fibrils by synthetic A beta analogues using a thioflavine-T assay for fibril formation, electron microscopy and Congo Red staining. Our results show that, under the conditions used, apoE directly promotes amyloid fibril formation, increasing both the rate of fibrillogenesis and the total amount of amyloid formed. ApoE accelerated fibril formation of both wild-type A beta-(1-40) and A beta-(1-40A), an analogue created by the replacement of valine with alanine at residue 18, which alone produces few amyloid-like fibrils. However, apoE produced only a minimal effect on A beta-(1-40Q), found in the Dutch variant of Alzheimer's disease. When recombinant apoE isoforms were used, apoE4 was more efficient than apoE3 at enhancing amyloid formation. These in vitro observations support the hypothesis that apoE acts as a pathological chaperone, promoting the beta-pleated-sheet conformation of soluble A beta into amyloid fibres, and provide a possible explanation for the association of the apoE4 genetic isoform with Alzheimer's disease.

PubMed Disclaimer

Cited by

Oligomeric Abeta in Alzheimer's disease: relationship to plaque and tangle pathology, APOE genotype and cerebral amyloid angiopathy.
van Helmond Z, Miners JS, Kehoe PG, Love S. van Helmond Z, et al. Brain Pathol. 2010 Mar;20(2):468-80. doi: 10.1111/j.1750-3639.2009.00321.x. Epub 2009 Jul 16. Brain Pathol. 2010. PMID: 19725829 Free PMC article.
Dimeric amyloid beta protein rapidly accumulates in lipid rafts followed by apolipoprotein E and phosphorylated tau accumulation in the Tg2576 mouse model of Alzheimer's disease.
Kawarabayashi T, Shoji M, Younkin LH, Wen-Lang L, Dickson DW, Murakami T, Matsubara E, Abe K, Ashe KH, Younkin SG. Kawarabayashi T, et al. J Neurosci. 2004 Apr 14;24(15):3801-9. doi: 10.1523/JNEUROSCI.5543-03.2004. J Neurosci. 2004. PMID: 15084661 Free PMC article.
In vivo effects of ApoE and clusterin on amyloid-beta metabolism and neuropathology.
Holtzman DM. Holtzman DM. J Mol Neurosci. 2004;23(3):247-54. doi: 10.1385/JMN:23:3:247. J Mol Neurosci. 2004. PMID: 15181253 Review.
The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption.
Legleiter J, Fryer JD, Holtzman DM, Kowalewski A. Legleiter J, et al. ACS Chem Neurosci. 2011 Oct 19;2(10):588-599. doi: 10.1021/cn2000475. ACS Chem Neurosci. 2011. PMID: 22125665 Free PMC article.
Relationship between plasma lipids and mild cognitive impairment in the elderly Chinese: a case-control study.
He Q, Li Q, Zhao J, Wu T, Ji L, Huang G, Ma F. He Q, et al. Lipids Health Dis. 2016 Sep 5;15(1):146. doi: 10.1186/s12944-016-0320-6. Lipids Health Dis. 2016. PMID: 27595570 Free PMC article.

References

1. Ann Neurol. 1994 Sep;36(3):434-7 - PubMed
1. Nature. 1994 Nov 3;372(6501):92-4 - PubMed
1. Neurobiol Aging. 1994 Mar-Apr;15(2):143-52 - PubMed
1. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131-5 - PubMed
1. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9 - PubMed

Fibrillogenesis in Alzheimer's disease of amyloid beta peptides and apolipoprotein E - PubMed (original) (raw)