NEW YORK (Reuters Health) - Gene delivery of human apolipoprotein E2 (apoE2) reduces the brain amyloid-beta burden in a mouse model of Alzheimer’s disease, according to a new report.
“We are making good progress in understanding the molecular events underlying the pathogenesis of Alzheimer’s disease,” Dr. Inder M. Verma from The Salk Institute, La Jolla, California told Reuters Health. “Gene therapy offers the opportunity to influence the progression of this horrible disease.”
Dr. Verma and colleagues investigated whether gene delivery of the three common human apoE isoforms (apoE2, apoE3, and apoE4) could directly alter the brain deposition of amyloid-beta in a transgenic (PDAPP) mouse model of Alzheimer’s disease.
Expression of apoE2 for 5 weeks resulted in a 30% to 50% reduction in amyloid-beta burden in the hippocampus of PDAPP mice, the team reports in the January 25th issue of the Proceedings of the National Academy of Sciences Early Edition, available online January 17th.
In contrast, the researchers note, expression of apoE4 resulted in a 2-3-fold increase in brain amyloid-burden in this mouse model.
“The rather robust effect of lenti-apoE2 treatment in reducing hippocampal amyloid-beta burden in PDAPP mice is also noteworthy in light of clinical-epidemiological data suggesting that the e2 allele is a protective genetic risk factor for Alzheimer’s disease,” the investigators explain.
“Thus, the protective effect of apoE2 on Alzheimer’s disease risk may in part be due to its ability to facilitate amyloid-beta clearance and/or degradation in the brain and to prevent the formation of neuritic plaques, one of the neuropathological hallmarks of the disease.”
Dr. Verma commented, “We would like to examine the effects of the lenti-apoE vectors/constructs on other aspects of Alzheimer’s pathology -- namely neurodegeneration, neurofibrillary tangle formation, and soluble A-beta oligomers.”
Beyond that, “We would also like to examine other animal models of Alzheimer’s disease,” the researcher added. “Finally, we need to elaborate the exact cellular/molecular mechanisms as to how apoE2 exerts its ‘therapeutic’ effects on A-beta/amyloid pathology.”
Source: PNAS 2005;102:1211-1216.doi:10.1073/pnas.0409072102. [ Google search on this article ]
MeSH Headings:Amyloid: Genetic Techniques: Mice, Inbred Strains: Investigative Techniques: Amyloid beta-Protein: Animals, Inbred Strains: Gene Transfer: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
