阿尔茨海默病中的炎症：性别和 APOE 因素重要吗？

Inflammation in Alzheimer's Disease: Do Sex and APOE Matter?

机构信息

Djavad Mowafaghian Centre for Brain Health and Department of Psychology, University of British Columbia, Vancouver, BC, Canada.

Women's Health Research Institute of British Columbia, Vancouver, BC, Canada.

出版信息

J Alzheimers Dis. 2020;78(2):627-641. doi: 10.3233/JAD-200982.

DOI:10.3233/JAD-200982

PMID:33016923

Abstract

BACKGROUND

Alzheimer's disease (AD) disproportionately affects females with steeper cognitive decline and more neuropathology compared to males, which is exacerbated in females carrying the APOEɛ4 allele. The risk of developing AD is also higher in female APOEɛ4 carriers in earlier age groups (aged 65-75), and the progression from cognitively normal to mild cognitive impairment (MCI) and to AD may be influenced by sex. Inflammation is observed in AD and is related to aging, stress, and neuroplasticity, and although studies are scarce, sex differences are noted in inflammation.

OBJECTIVE

The objective of this study was to investigate underlying physiological inflammatory mechanisms that may help explain why there are sex differences in AD and APOEɛ4 carriers.

METHODS

We investigated, using the ADNI database, the effect of sex and APOE genotype (non-carriers or carriers of 1 and 2 APOEɛ4 alleles) and sex and diagnosis (cognitively normal (CN), MCI, AD) on CSF (N = 279) and plasma (N = 527) markers of stress and inflammation.

RESULTS

We found CSF IL-16 and IL-8 levels differed by sex and APOE genotype, as IL-16 was higher in female APOEɛ4 carriers compared to non-carriers, while the opposite pattern was observed in males with IL-8. Furthermore, females had on average higher levels of plasma CRP and ICAM1 but lower levels of CSF ICAM1, IL-8, IL-16, and IgA than males. Carrying APOEɛ4 alleles and diagnosis (MCI and AD) decreased plasma CRP in both sexes.

CONCLUSION

Sex and APOE genotype differences in CSF and plasma inflammatory biomarkers support that the underlying physiological changes during aging differ by sex and tissue origin.

摘要

背景

阿尔茨海默病（AD）女性患者的认知衰退速度比男性更快，神经病理学表现更严重，尤其在携带 APOEɛ4 等位基因的女性中更为明显。女性 APOEɛ4 携带者在年龄较小的（65-75 岁）群体中患上 AD 的风险更高，从认知正常到轻度认知障碍（MCI）再到 AD 的进展可能受到性别影响。AD 中存在炎症，与衰老、压力和神经可塑性有关，尽管相关研究较少，但炎症存在性别差异。

目的

本研究旨在探究潜在的生理性炎症机制，以帮助解释 AD 和 APOEɛ4 携带者中存在性别差异的原因。

方法

我们利用 ADNI 数据库，研究了性别和 APOE 基因型（非携带者或携带 1 个和 2 个 APOEɛ4 等位基因）以及性别和诊断（认知正常（CN）、MCI、AD）对 CSF（N=279）和血浆（N=527）应激和炎症标志物的影响。

结果

我们发现 CSF 中 IL-16 和 IL-8 水平存在性别和 APOE 基因型差异，女性 APOEɛ4 携带者的 IL-16 水平高于非携带者，而男性的 IL-8 水平则呈现相反的模式。此外，女性的血浆 CRP 和 ICAM1 水平平均高于男性，但 CSF ICAM1、IL-8、IL-16 和 IgA 水平低于男性。携带 APOEɛ4 等位基因和诊断（MCI 和 AD）会降低两性的血浆 CRP 水平。