(P27-006-23) Brain Alpha-Tocopherol Stereoisomer Profile Is Associated With Body Mass Index and Alzheimer’s Disease Pathology in Centenarians

Objectives: By utilizing the data collected and obtained from the Georgia Centenarian Study (GCS), this study aimed to investigate the relationship of specific α-tocopherol (αT) stereoisomers in the brain of older adults with global cognitive status and Alzheimer’s disease (AD) pathology.

Methods: This study utilized data and brain tissues (temporal cortex) of 47 decedents from the GCS study. Global Deterioration Scale (GDS) was assessed within one year of mortality for all subjects. AD pathology assessment was carried out at autopsy, which included diffuse plaques (DP), neuritic plaques (NP), and neurofibrillary tangle (NFT). Brain tocopherol stereoisomer profiles in the temporal cortex were analyzed with chiral HPLC. Spearman's correlation analyses and partial correlation analyses were used to examine the correlations between brain tocopherol concentrations and AD pathology.

Results: RRR-αT was the predominant stereoisomer, accounting for >50% of total αT concentration in 42 subjects. BMI was positively correlated with %RRR-αT (ρ = 0.34, p = 0.021), but was negatively associated with %RSS-αT (ρ = -0.45, p = 0.002). After adjusting for sex, race, education, ApoE genotype, diabetes and hypertension, higher %RRR-αT was associated with lower DP and NFT counts in different brain regions (p < 0.10). In contrast to these favorable associations, %RSS-αT was positively correlated with DP and NFT counts across brain regions (p < 0.10). By including BMI in the partial correlation analysis, the negative correlations of %RRR and the positive correlations of %RSS with AD pathologies were largely abolished.

Conclusions: RRR-αT was the predominant form of αT stereoisomers in the brain of the oldest old. This study found no significant relationships between the absolute concentrations of any αT stereoisomers and AD pathology. However, the proportion of two specific stereoisomers, RRR- and RSS-αT, did show significant and consistent correlations with AD pathology in different brain regions. %RRR-αT was found to be inversely correlated with AD pathology, while %RSS-αT was positively correlated with AD pathology. This exploratory study serves as a foundation for future research on the impact of different αT stereoisomers on cognitive function in aging.

Funding Sources: This research was funded by Abbott Nutrition.