RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimer's Disease

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain regions (Brodmann's Area 9, hippocampus, inferior parietal lobule, and the superior and middle temporal gyri), we found that the RNA adduct 8-hydroxyguanine (8-OHG) decreased, while 8-hydroxyadenine (8-OHA) increased in AD. The cerebellum, which is generally spared in AD, did not show disease related changes, and no RNA adducts correlated with the number of plaques or tangles. Multiple regression analysis revealed that SDS-soluble Aβ42 was the best predictor of changes in 8-OHG, while formic acid-soluble Aβ42 was the best predictor of changes in 8-OHA. This study indicates that although there is a connection between AD related neuropathology and RNA oxidation, this relationship is not straightforward

From the Atomistic to the Macromolecular Scale: Distinct Simulation Approaches for Polyelectrolyte Solutions

Polyelectrolytes reveal interesting properties in solution. At short length scales,the dissociation of counterions is heavily affected by the chemical structure of thepolyelectrolyte, the properties of the solution, and specific ion effects. At largerlength scales, the structure of polyelectrolyte solutions is dominated by long-range interactions. In the special case of dissolved polyanions and polycations,polyelectrolyte complexes or multilayers can form. In this review we presentdistinct simulation approaches to study the corresponding effects at differentlength scales in more detail. Whereas at short length scales, atomistic moleculardynamics simulation is often the method of choice, semi-coarse-grained and coarse-grained models with a lower level of details reveal their benefits at largerlength scales