C. N. BASSETT, T. J. MONTINE*

University of Montevallo, Department of Biology, Chemistry, and Mathematics, Montevallo, AL 35115 and *Vanderbilt University Medical Center, Departments of Pathology, Pharmacology, and Center for Neurosciences, Nashville, TN 37232. Correspondence: Thomas J. Montine, MD, PhD, VUMC Department of Pathology, 21st Ave. S. @ Garland, C3321A Medical Center North, Nashville, TN 37232, USA. Phone 615-343-5841. Fax 615-343-7089. Email: tom.montine@mcmail.vanderbilt.edu o This work was supported by NIH grants AG00774 and AG16835

Alzheimer's Disease (AD) is a clinical-pathological entity that probably derives from different causes. Mounting evidence strongly implicates regionally increased oxidative damage to brain beyond what occurs with aging as one of the processes that may contribute to AD progression. While several different classes of molecules may be affected, lipid peroxidation is thought to be a prominent and especially deleterious form of oxidative damage in brain due to this organ's relative enrichment in polyunsaturated fatty acids. Our laboratory recently has demonstrated that lipoproteins in AD brain extracellular fluid are more vulnerable to oxidation than lipoproteins in control brain extracellular fluid. Apolipoprotein E (apoE) is the principal apolipoprotein in the central nervous system (CNS), and it serves as the major apolipoprotein that is capable of lipid transport and regulation of lipid metabolism through known receptor-mediated processes. Moreover, inheritance of the APOE4 allele represents the strongest genetic risk factor for sporadic AD. Evidence suggests that apoE isoforms may specifically influence the cellular distribution of lipid peroxidation products in brain and may therefore contribute to the stratification of risk for AD associated with APOE. Here, we review possible mechanisms whereby lipoprotein trafficking and lipid peroxidation converge to contribute to neurodegeneration in AD brain.

Keywords: Alzheimer's disease, aging, lipoproteins, apoE, lipid peroxidation, neurodegeneration, nutrition, elderly.