Chan Jia Pei, Tanprasertsuk Jirayu, Johnson Elizabeth J, Dey Priyankar, Bruno Richard S, Johnson Mary Ann, Poon Leonard W, Davey Adam, Woodard John L, Kuchan Matthew J
Abbott Nutrition, Columbus, OH 43219, USA.
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA.
Antioxidants (Basel). 2024 Aug 17;13(8):997. doi: 10.3390/antiox13080997.
Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, -αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. % was inversely correlated with DPs in the frontal cortex (FC) (ρ = -0.35, = 0.032) and TC (ρ = -0.34, = 0.038). % (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, = 0.017) and with NFTs in the FC (ρ = 0.37, = 0.024), TC (ρ = 0.42, = 0.009), and amygdala (ρ = 0.43, = 0.008) after controlling for covariates. Neither nor -αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %-αT (ρ = 0.34, = 0.021) and %-αT (ρ = -0.45, = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship.
先前有报道称，百岁老人特定脑结构中的脑α-生育酚（αT）浓度与神经原纤维缠结（NFT）计数呈负相关。然而，天然或合成αT立体异构体对这种关系的贡献尚不清楚。在本研究中，对佐治亚百岁老人研究中47名百岁老人（年龄：102.2±2.5岁，体重指数：22.1±3.9kg/m）颞叶皮质（TC）中的αT立体异构体进行了定量，然后将其与七个脑区中的淀粉样斑块（弥漫性和神经炎斑块；DPs、NPs）和NFTs进行关联。天然立体异构体-αT是所有受试者中的主要立体异构体，除五名受试者外，在所有受试者中占总αT的比例均超过50%。%-αT与额叶皮质（FC）（ρ=-0.35，P=0.032）和TC（ρ=-0.34，P=0.038）中的DPs呈负相关。在控制协变量后，%-αT（一种合成αT立体异构体）与TC中的DPs呈正相关（ρ=0.39，P=0.017），与FC（ρ=0.37，P=0.024）、TC（ρ=0.42，P=0.009）和杏仁核（ρ=0.43，P=0.008）中的NFTs呈正相关。无论是-αT还是-αT均与生前整体认知无关。即使在体重指数范围狭窄且正常的情况下，体重指数仍与%-αT（ρ=0.34，P=0.021）和%-αT（ρ=-0.45，P=0.002）相关。这些结果首次描述了百岁老人TC中αT立体异构体谱，表明特定αT立体异构体在脑中的积累会影响DP和NFT计数，但不会影响生前整体认知。需要进一步研究以证实这些发现，并确定体重指数在介导这种关系中的潜在作用。
