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维生素D可提高轻度认知障碍患者的血浆β淀粉样蛋白1-40水平并保护淋巴细胞免于氧化死亡。

Vitamin D Increases Aβ140 Plasma Levels and Protects Lymphocytes from Oxidative Death in Mild Cognitive Impairment Patients.

作者信息

SanMartin Carol D, Henriquez Mauricio, Chacon Carlos, Ponce Daniela P, Salech Felipe, Rogers Nicole K, Behrens Maria I

机构信息

Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santiago, Chile

Center for Integrative Biology, Universidad Mayor, Santiago, Chile

出版信息

Curr Alzheimer Res. 2018;15(6):561-569. doi: 10.2174/1567205015666171227154636.

Abstract

BACKGROUND

Mild cognitive impairment (MCI) has an increased rate of progression to dementia. Alterations of some metabolic factors, such as deficiency of vitamin D, are a risk factor for cognitive deterioration. Vitamin D is involved in the clearance of β-amyloid (Aβ) from the brain. We have reported that lymphocytes from Alzheimer's disease (AD) patients have an increased susceptibility to oxidative death by H2O2 exposure, but currently it is unknown if this characteristic is modifiable in vivo.

OBJECTIVE

To determine if correction of low vitamin D levels protects lymphocytes from oxidative death and increases Aβ1-40 plasma levels in MCI and very early AD (VEAD) patients.

METHOD

Sixteen MCI, 11 VEAD and 25 healthy control (HC) voluntaries were evaluated with the Clinical Dementia Rating (CDR), Montreal Cognitive assessment (MoCA), and Memory Index score (MIS). Lymphocyte death was measured by flow cytometry after 20h exposure to H2O2. In patients with low levels of vitamin D -11 MCI, 9 VEAD and 20 HC- lymphocyte H2O2-death, plasma Aβ1-40 levels and cognitive status were evaluated pre- and post-vitamin D supplementation for 6 months.

RESULTS

Lymphocytes from MCI and VEAD patients showed increased susceptibility to oxidative death at study entry. In MCI, but not VEAD patients, lymphocyte susceptibility to death and Aβ1-40 levels plasma levels improved after 6 months of vitamin D supplementation. In addition, cognitive status on follow-up (18 months) improved in MCI patients after vitamin D supplementation.

CONCLUSION

Vitamin D supplementation may be beneficial in MCI. The lack of effect in VEAD may be due to a more advanced stage or different characteristics of the neurodegenerative process.

摘要

背景

轻度认知障碍(MCI)进展为痴呆的速率增加。一些代谢因素的改变,如维生素D缺乏,是认知功能恶化的危险因素。维生素D参与大脑中β-淀粉样蛋白(Aβ)的清除。我们曾报道,阿尔茨海默病(AD)患者的淋巴细胞在暴露于过氧化氢时对氧化死亡的易感性增加,但目前尚不清楚这种特征在体内是否可改变。

目的

确定纠正低维生素D水平是否能保护MCI和极早期AD(VEAD)患者的淋巴细胞免于氧化死亡,并提高血浆Aβ1-40水平。

方法

对16名MCI患者、11名VEAD患者和25名健康对照(HC)志愿者进行临床痴呆评定量表(CDR)、蒙特利尔认知评估量表(MoCA)和记忆指数评分(MIS)评估。淋巴细胞在暴露于过氧化氢20小时后通过流式细胞术测量死亡情况。在维生素D水平低的患者中——11名MCI患者、9名VEAD患者和20名HC患者——在补充维生素D 6个月前后评估淋巴细胞过氧化氢诱导的死亡、血浆Aβ1-40水平和认知状态。

结果

在研究开始时,MCI和VEAD患者的淋巴细胞对氧化死亡的易感性增加。在MCI患者中,而非VEAD患者中,补充维生素D 6个月后淋巴细胞对死亡的易感性和血浆Aβ1-40水平有所改善。此外,补充维生素D后,MCI患者随访18个月时的认知状态有所改善。

结论

补充维生素D可能对MCI有益。在VEAD患者中缺乏效果可能是由于神经退行性过程处于更晚期或具有不同特征。

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