Travassos Maria, Santana Isabel, Baldeiras Inês, Tsolaki Magda, Gkatzima Olymbia, Sermin Genc, Yener Görsev G, Simonsen Anja, Hasselbalch Steen G, Kapaki Elisabeth, Mara Bourbouli, Cunha Rodrigo A, Agostinho Paula, Blennow Kaj, Zetterberg Henrik, Mendes Vera M, Manadas Bruno, de Mendon Alexandreça
Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Department of Neurology, Coimbra University Hospital, Coimbra, Portugal.
J Alzheimers Dis. 2015;47(4):1069-78. doi: 10.3233/JAD-150374.
Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau in the CSF were determined using sandwich ELISA methods and other Aβ species, Aβ(X-38), Aβ(X-40), and Aβ(X-42), with the MSD Aβ Triplex assay. The concentration of caffeine was 0.79±1.15 μg/mL in the CSF and 1.20±1.88 μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ42 in the CSF. Theobromine in the CSF was positively correlated with the levels of other xanthines in the CSF, but not in the plasma, suggesting that it may be formed by central metabolic pathways. In conclusion, caffeine consumption does not modify the levels of CSF biomarkers, and does not require to be controlled for when measuring CSF biomarkers in a clinical setting. Since theobromine is associated with a favorable Aβ profile in the CSF, the possibility that it might have a protective role in AD should be further investigated.
咖啡因可能通过调节淀粉样蛋白-β（Aβ）代谢途径对阿尔茨海默病（AD）起到保护作用。本研究旨在探讨咖啡因摄入量与脑脊液（CSF）生物标志物，尤其是Aβ之间可能存在的关联。该研究纳入了88例AD或轻度认知障碍患者。使用经过验证的食物问卷评估咖啡因和可可碱的摄入量。采用液相色谱-串联质谱法对咖啡因及其主要活性代谢物进行定量分析。使用夹心酶联免疫吸附测定法测定CSF中A（1-42）、总tau蛋白和磷酸化tau蛋白的水平，并用MSD Aβ三联检测法测定其他Aβ种类，即Aβ（X-38）、Aβ（X-40）和Aβ（X-42）。CSF中咖啡因浓度为0.79±1.15μg/mL，血浆中为1.20±1.88μg/mL。未发现咖啡因摄入量与CSF中Aβ42之间存在相关性。然而，发现CSF和血浆中可可碱浓度与CSF中Aβ42之间存在显著正相关。CSF中的可可碱与CSF中其他黄嘌呤的水平呈正相关，但与血浆中无关，这表明它可能是由中枢代谢途径形成的。总之，咖啡因摄入量不会改变CSF生物标志物的水平，在临床环境中测量CSF生物标志物时无需对其进行控制。由于可可碱与CSF中有利的Aβ谱相关，应进一步研究其在AD中可能具有保护作用的可能性。
