Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France.
Gérontopôle, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France; UMR1027 INSERM, Université de Toulouse III Paul Sabatier, Toulouse, France.
Exp Gerontol. 2018 Jul 15;108:226-230. doi: 10.1016/j.exger.2018.04.014. Epub 2018 Apr 25.
Inflammation promotes amyloidogenesis in animals and markers of inflammation are associated with β-amyloid (Aβ) in humans. Hence, we sought to examine the cross-sectional associations between chronically elevated plasma C reactive protein (CRP) and cortical Aβ in 259 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial (MAPT).
Cortical-to-cerebellar standard uptake value ratios were obtained using [F] florbetapir positron emission tomography (PET). CRP was measured in plasma using immunoturbidity. Chronically raised CRP was defined as having 2 consecutively high CRP readings (>3 mg/l ≤ 10 mg/l) between study baseline and the 1 year visit (visits were performed at baseline, 6 months, 1 year and then annually). Associations were explored using adjusted multiple linear regression.
Chronically raised CRP was found to be inversely associated with cortical Aβ (B-coefficient: -0.054, SE: 0.026, p = 0.040) and this association seemed to be specific to apolipoprotein E (Apo E) ε4 carriers (B-coefficient: -0.130, SE: 0.058, p = 0.027). CRP as an isolated reading measured closest to PET scan was also inversely associated with cortical Aβ when CRP was treated as a dichotomized variable (high CRP > 3 mg/l ≤ 10 mg/l, B-coefficient: -0.048, SE: 0.023, p = 0.043).
Our preliminary findings suggest that inflammation might be beneficial in the early stages of Alzheimer's disease as the immune systems attempts to combat Aβ pathology particularly in ApoE ε4 carriers. Investigating the temporal relationships between cerebral Aβ and a panel of inflammatory markers would provide further evidence as to whether chronic inflammation might modulate amyloidogenesis in vivo.
在动物中，炎症会促进淀粉样蛋白形成，而炎症标志物与人类的β-淀粉样蛋白（Aβ）有关。因此，我们试图在 259 名报告有主观记忆问题且无痴呆的老年人中，检查慢性高血浆 C 反应蛋白（CRP）与多领域阿尔茨海默病预防试验（MAPT）中皮质 Aβ 之间的横断面关联。
使用[F]氟比洛芬正电子发射断层扫描（PET）获得皮质-小脑标准摄取比值。使用免疫比浊法测量血浆中的 CRP。在研究基线和第 1 年就诊期间，CRP 连续 2 次升高（就诊时间为基线、6 个月、1 年，然后每年一次），定义为慢性 CRP 升高。使用调整后的多元线性回归法探索相关性。
发现慢性 CRP 与皮质 Aβ呈负相关（B 系数：-0.054，SE：0.026，p=0.040），这种相关性似乎只存在于载脂蛋白 E（ApoE）ε4 携带者中（B 系数：-0.130，SE：0.058，p=0.027）。当 CRP 作为二分类变量处理时，最接近 PET 扫描时测量的 CRP 孤立读数与皮质 Aβ也呈负相关（高 CRP>3mg/l≤10mg/l，B 系数：-0.048，SE：0.023，p=0.043）。
我们的初步研究结果表明，在阿尔茨海默病的早期阶段，炎症可能是有益的，因为免疫系统试图对抗 Aβ 病理学，尤其是在 ApoE ε4 携带者中。研究脑内 Aβ 与一组炎症标志物之间的时间关系，将进一步证明慢性炎症是否会在体内调节淀粉样蛋白形成。
