大脑α-生育酚浓度与Braak早期阶段受影响脑区的神经原纤维缠结计数呈负相关：一项针对高龄老人的横断面研究结果

Brain Α-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.

作者信息

Tanprasertsuk J, Scott T M, Johnson M A, Poon L W, Nelson P T, Davey A, Woodard J L, Vishwanathan R, Barbey A K, Barger K, Wang X-D, Johnson E J

机构信息

Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, 02111, United States of America.

Department of Nutrition and Health Sciences, University of Nebraska Lincoln, Lincoln, NE, 68583, United States of America.

出版信息

JAR Life. 2021 Feb 12;10:8-16. doi: 10.14283/jarlife.2021.2. eCollection 2021.

DOI:10.14283/jarlife.2021.2

PMID:36923512

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10002902/

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 α- and γ-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 α- and γ-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 α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (β = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (β = -2.01, 95% CI [-3.72, -0.30]), hippocampus (β = -2.23, 95% CI [-3.82, -0.64]), and subiculum (β = -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 α-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). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed.

CONCLUSIONS

Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

摘要

目的

较高的维生素E水平与较低的阿尔茨海默病（AD）风险相关。然而，神经组织中维生素E浓度与AD病理之间关联的证据有限。

设计

研究了人脑中α-生育酚和γ-生育酚浓度与AD病理严重程度——神经原纤维缠结（NFT）和神经炎性斑块（NP）——之间的横断面关系。

设置与参与者

收集了参与佐治亚百岁老人研究第三阶段的43名百岁老人（死亡时≥98岁）的大脑进行尸检。

测量

大脑α-生育酚和γ-生育酚浓度（先前已报告）取额叶、颞叶和枕叶皮质的平均值。NP和NFT计数（先前已报告）在额叶、颞叶、顶叶、内嗅皮质、杏仁核、海马体和下托进行评估。使用Braak分期评估NFT的拓扑进展。进行多元线性回归以评估生育酚浓度与NP或NFT计数之间的关系，同时对协变量进行调整或不调整。

结果

大脑α-生育酚浓度与杏仁核（β = -2.67，95%置信区间[-4.57, - 0.79]）、内嗅皮质（β = -2.01，95%置信区间[-3.72, -0.30]）、海马体（β = -2.23，95%置信区间[-3.82, -0.64]）和下托（β = -2.52，95%置信区间[-4.42, -0.62]）中的NFT计数呈负相关，这些脑区中NFT在拓扑进展中出现较早，但在新皮质中并非如此。Braak III-IV期的受试者α-生育酚水平（中位数 = 69,622 pmol/g，四分位数间距 = 54,389 - 72,155 pmol/g）低于Braak I-II期的受试者（中位数 = 72,108 pmol/g, 四分位数间距 = 64,056 - 82,430 pmol/g）, 但差异具有临界显著性（p = 0.063）。在评估的任何脑区中，γ-生育酚浓度与NFT或NP计数均无关联。