Poster Presentations

Session Title: Apolipoprotein-E
Presentation Date: Thursday, March 12 – Friday, March 13 ,2009

APOE COUNTERACTS THE IMPAIRMENT OF MITOCHONDRIAL ACTIVITY INDUCED BY OLIGOMERIC Aß-(1-42)

K. Sorensen, O. Jorgensen
Institute of Neuroscience and Pharmacology, University of Copenhagen, Laboratory of Neuropsychiatry, Copenhagen, Denmark

Alzheimer's disease (AD) is the most prevalent type of dementia in old age but the mechanisms leading to AD are not yet established. Overexpression of oligomeric amyloid-ß-peptides (Aß-(1-42) oligomers) probably are of importance for initiation of AD and may mediate mitochondrial dysfunction.
We studied primary neuronal cultures from newborn rat hippocampi. To measure the mitochondrial activity in live cells we used the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromid-assay (MTT-assay) and found that Aß-(1-42) oligomers strongly impaired mitochondrial activity.
The E4 isoform of the apolipoprotein E gene (APOE4) is known to be a major risk factor for AD. Recombinant apoE isoforms apoE2, apoE3 and apoE4 were investigated regarding to their interaction with Aß-(1-42) oligomers. Added to the cultures, the isoforms strongly diminished the reduction in mitochondrial activity induced by Aß-(1-42) oligomers. Surprisingly, all three isoforms were equipotent in counteracting the impairment of mitochondrial activity.
Studies on human brain homogenates indicate that apoE levels are dependent on the APOE genotype (data will be presented).
The results obtained in this study support the presumption that Aß-(1-42) oligomers reduce mitochondrial activity in AD. Furthermore, the role of APOE4 as a risk factor in AD may reside in reduced expression or increased degradation of the gene product.