Table 1.
Summary of Subject Demographic Data.
Figure 1.
Flowchart depicting the steps comprising the data analysis.
A directed analysis of the data was used to reduce the large data set to its significant components. A multivariate analysis determined which variables were significantly different in AD using PMI and age as covariates and gender as a variable; only significant variables were included in further analysis. A Spearman correlation was used to determine the relationships between the five RNA adducts of interest and the other measures of AD pathology. Finally, these significant variables were analyzed by stepwise multiple regression to determine if they predicted the changes in the RNA adducts.
Figure 2.
8-OHG and 8-OHA change in opposite directions in the late-stage AD brain.
The 8-OHG adduct decreased (p = 0.046) in the disease state, whereas the 8-OHA adduct increased in AD brain (p = 0.038). Data are expressed as the number of oxidatively modified bases per 1000 bases of total RNA. The analysis included gender, age and PMI. Values were averaged over several disease-affected brain regions (c.f. Table 1); no significant changes were seen in cerebellum. NCI: No Cognitive Impairment; AD: Alzheimer's disease. Rotated Hourglass: mean.
Figure 3.
Oxidation adducts are modeled by single but separate pools of Aβ.
Using multiple stepwise regression, the decrease in 8-OHG was correlated to SDS-soluble Aβ42 (top; adj-R2 = 0.257; p<0.01) while the increase in 8-OHA lesions was correlated to formic acid-soluble Aβ42 (bottom; adj-R2 = 0.141; p<0.05). Data are expressed as the number of oxidatively modified bases per 1000 bases of total RNA. Open Symbol: NCI; Closed Symbol: AD.