QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 6, 2005, 25(14):3621-3627; doi:10.1523/JNEUROSCI.4213-04.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Wilhelmus, M. M. M. Articles by Verbeek, M. M. Search for Related Content PubMed PubMed Citation Articles by Wilhelmus, M. M. M. Articles by Verbeek, M. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Apolipoprotein E Genotype Regulates Amyloid- Cytotoxicity

Micha M. M. Wilhelmus,^1,2 Irene Otte-Höller,² Judianne Davis,³ William E. Van Nostrand,³ Robert M. W. de Waal,² and Marcel M. Verbeek^1,2

Departments of ¹Neurology and ²Pathology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands, and ³Department of Medicine, Health Sciences Center, Stony Brook University, Stony Brook, New York 11794-8153

The 4 allele of apolipoprotein E (ApoE) is a risk factor for Alzheimer's disease (AD), whereas the 2 allele may be relatively protective. Both alleles are risk factors for cerebral amyloid angiopathy (CAA)-related hemorrhages. CAA is associated with degeneration of smooth muscle cells and pericytes. Previously, we described that synthetic amyloid-_1-40 peptide (A_1-40) with the ²²Glu Gln "Dutch" mutation caused pericyte death in vitro by a mechanism that involves A fibril-like assembly at the cell surface. It is known that ApoE binds to A and may modify its biological activities. In the present study, we evaluated the effect of ApoE on A-mediated toxicity of cerebrovascular cells. We observed that cultured cells with an 4/4 genotype were more vulnerable to A than cultures with an 3/3 or 3/4 genotype. The one cell culture with the 2/3 genotype was relatively resistant to A compared with other cultures. Furthermore, we observed a dose-dependent protective effect of native ApoE against A-mediated toxicity of cerebrovascular cells and, in addition, ApoE 2/3 cells secreted more ApoE protein compared with cells with other ApoE genotypes, in particular, compared with 4/4 cells. Thus, the disparity between ApoE genotype and A-mediated toxicity might be related to differences in the cellular capacity to secrete ApoE. The present data suggest that one mechanism by which ApoE may alter the risk for AD is a genotype-dependent regulation of A cytotoxicity, possibly via variations in its secretion levels, whereby extracellular ApoE may bind to A and thereby modify A-mediated cell death.

Key words: apolipoprotein E; Alzheimer's disease; amyloid- protein; cerebrovascular cells; CAA; cytotoxicity

---

Received Oct 11, 2004; revised February 21, 2005; accepted February 23, 2005.

This article has been cited by other articles:

				F. Xu, M. P. Vitek, C. A. Colton, M. L. Previti, N. Gharkholonarehe, J. Davis, and W. E. Van Nostrand Human Apolipoprotein E Redistributes Fibrillar Amyloid Deposition in Tg-SwDI Mice J. Neurosci., May 14, 2008; 28(20): 5312 - 5320. [Abstract] [Full Text] [PDF]

				M. M.M. Wilhelmus, I. Otte-Holler, J. J.J. van Triel, R. Veerhuis, M. L.C. Maat-Schieman, G. Bu, R. M.W. de Waal, and M. M. Verbeek Lipoprotein Receptor-Related Protein-1 Mediates Amyloid- -Mediated Cell Death of Cerebrovascular Cells Am. J. Pathol., December 1, 2007; 171(6): 1989 - 1999. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help