| First Author | Manelli AM | Year | 2007 |
| Journal | Neurobiol Aging | Volume | 28 |
| Issue | 8 | Pages | 1139-47 |
| PubMed ID | 16837105 | Mgi Jnum | J:123898 |
| Mgi Id | MGI:3719943 | Doi | 10.1016/j.neurobiolaging.2006.05.024 |
| Citation | Manelli AM, et al. (2007) Abeta42 neurotoxicity in primary co-cultures: effect of apoE isoform and Abeta conformation. Neurobiol Aging 28(8):1139-47 |
| abstractText | Autosomal dominant mutations that increase amyloid-beta(1-42) (Abeta42) cause familial Alzheimer's disease (AD), and the most common genetic risk factor for AD is the presence of the epsilon4 allele of apolipoprotein E (apoE). Previously, we characterized stable preparations of Abeta42 oligomers and fibrils and reported that oligomers induced a 10-fold greater increase in neurotoxicity than fibrils in Neuro-2A cells. To determine the effects of apoE genotype on Abeta42 oligomer- and fibril-induced neurotoxicity in vitro, we co-cultured wild type (WT) neurons with glia from WT, apoE-knockout (apoE-KO), and human apoE2-, E3-, and E4-targeted replacement (TR) mice. Dose-dependent neurotoxicity was induced by oligomeric Abeta42 with a ranking order of apoE4-TR>KO=apoE2-TR=apoE3-TR>WT. Neurotoxicity induced by staurosporine or glutamate were not affected by apoE genotype, indicating specificity for oligomeric Abeta42-induced neurotoxicity. These in vitro data demonstrate a gain of negative function for apoE4, synergistic with oligomeric Abeta42, in mediating neurotoxicity. |
