Helen Wills Neuroscience Institute, University of California Berkeley, CA, USA.
Curr Alzheimer Res. 2013 Jan;10(1):48-56.
Previous studies have demonstrated alterations in the peripheral cholinergic system in Alzheimer's disease (AD), though results have been inconsistent and not linked to in vivo biomarkers of pathology. We examined the relationship between amyloid-beta (Aβ) plaques and plasma cholinesterase activity in a heterogeneous dementia population.
29 participants with clinical AD and 35 with non-AD diagnoses underwent positron emission tomography (PET) with the amyloid ligand [11C] PIB and plasma measurements of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Multi-linear regression was used to evaluate the relationship between AChE or BChE activity and PIB binding (adjusted for age, sex, apolipoprotein E4 and vascular risk), applying voxel-wise and region of interest (ROI) approaches. AChE activity was further adjusted for cholinesterase inhibitor (ChE-I) use. Global amyloid load was measured using a PIB Index, representing mean tracer binding in frontal, parietal, lateral temporal and cingulate cortex.
AChE activity was correlated with PIB Index (β=0.39, p < 0.001) and with regional PIB binding in frontal, temporal, parietal and occipital lobes, precuneus and posterior cingulate on both voxel-wise (p < 0.001 uncorrected) and ROI (β=0.26-0.41, p < 0.005) analysis. Correlations remained significant after covarying clinical diagnosis (β=0.42, p=0.001), and among participants naive to ChE-I (β=0.51, p=0.005). No correlation was found between BChE activity and PIB. Among AD participants, disease severity was not correlated with AChE, BChE or PIB Index.
AChE activity in plasma is correlated with brain Aβ load. Activation of the 'anti-inflammatory cholinergic pathway' may provide the link between Aβ plaques and peripheral cholinergic measures.
先前的研究表明，阿尔茨海默病（AD）患者外周胆碱能系统发生改变，但其结果不一致，且与病理学的体内生物标志物无关。我们在一个混杂的痴呆患者群体中检查了淀粉样β（Aβ）斑块与血浆胆碱酯酶活性之间的关系。
29 名临床 AD 患者和 35 名非 AD 诊断患者接受了正电子发射断层扫描（PET）与淀粉样蛋白配体 [11C] PIB 和血浆乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）活性的测量。多线性回归用于评估 AChE 或 BChE 活性与 PIB 结合之间的关系（调整年龄、性别、载脂蛋白 E4 和血管风险），并应用体素和感兴趣区域（ROI）方法。AChE 活性进一步调整了胆碱酯酶抑制剂（ChE-I）的使用。使用 PIB 指数测量整体淀粉样负荷，代表额叶、顶叶、外侧颞叶和扣带回皮质的平均示踪剂结合。
AChE 活性与 PIB 指数（β=0.39，p<0.001）以及额叶、颞叶、顶叶和枕叶、楔前叶和后扣带回的区域 PIB 结合呈正相关，在体素（p<0.001 未校正）和 ROI（β=0.26-0.41，p<0.005）分析中均如此。在协变量临床诊断（β=0.42，p=0.001）和 ChE-I 无经验参与者（β=0.51，p=0.005）中，相关性仍然显著。BChE 活性与 PIB 之间无相关性。在 AD 参与者中，疾病严重程度与 AChE、BChE 或 PIB 指数均无相关性。
血浆中的 AChE 活性与脑内 Aβ负荷相关。“抗炎胆碱能途径”的激活可能为 Aβ斑块与外周胆碱能测量之间提供联系。
