Brain a-tocopherol concentration is inversely associated with neurofibrillary tangle counts in brain regions affected in earlier BRAAK stages: a cross-sectional finding in the oldest OLD

Authors: TANPRASERTSUK, J - Tufts University; SCOTT, T.M. - Tufts University; JOHNSON, MARY ANN - University Of Nebraska; POON, LEONARD - University Of Georgia; NELSON, P.T. - University Of Kentucky; DAVEY, A. - University Of Delaware; WOODARD, J.L. - Wayne State University; VISHWANATHAN, R. - Tufts University; BARBEY, ARON - University Of Illinois; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JOHNSON, ELIZABETH - Tufts University

Submitted to: Journal of Aging Research & Lifestyle
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2020
Publication Date: 2/12/2021
Citation: Tanprasertsuk, J., Scott, T., Johnson, M., Poon, L., Nelson, P., Davey, A., Woodard, J., Vishwanathan, R., Barbey, A.K., Barger, K., Wang, X., Johnson, E.J. 2021. Brain a-tocopherol concentration is inversely associated with neurofibrillary tangle counts in brain regions affected in earlier BRAAK stages: a cross-sectional finding in the oldest OLD. Journal of Aging Research & Lifestyle. 10:8-16. https://doi.org/10.14283/jarlife.2021.2.
DOI: https://doi.org/10.14283/jarlife.2021.2

Interpretive Summary: Higher vitamin E intake has been associated with lower risk of Alzheimer's disease (AD). We characterized the relationship between vitamin E (a-tocopherol) concentrations and the severity of AD pathologies (called neurofibrillary tangle counts) in the brain of centenarians. We found that higher brain a-tocopherol concentrations were associated with lower neurofibrillary tangle counts in brain regions affected at earlier stage, not in brain regions affected at later stage, of AD. Our finding suggests the importance of a-tocopherol intervention timing at the early course of AD.

Technical Abstract: Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer's disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of a- and y-tocopherol and the severity of AD pathologies - neurofibrillary tangle (NFT) and neuritic plaque (NP) - was investigated. Setting & Participants: Brains from 43 centenarians (>= 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain a- and y-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain a-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (B= -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (B = -2.01, 95% CI [-3.72, -0.30]), hippocampus (B=-2.23, 95% CI [-3.82, -0.64]), and subiculum (B= -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower a-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). y-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain a-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of a-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.