Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer’s Disease?

Article type: Research Article

Authors: Travassos, Maria^a | Santana, Isabel^b | Baldeiras, Inês^c | Tsolaki, Magda^d | Gkatzima, Olymbia^d | Sermin, Genc^e | Yener, Görsev G.^e | Simonsen, Anja^f | Hasselbalch, Steen G.^f | Kapaki, Elisabeth^g | Mara, Bourbouli^g | Cunha, Rodrigo A.^c | Agostinho, Paula^c | Blennow, Kaj^h | Zetterberg, Henrik^h | Mendes, Vera M.ⁱ | Manadas, Brunoⁱ | de Mendon, Alexandreça^{a; *}

Affiliations: [a] Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Lisbon, Portugal | [b] Department of Neurology, Coimbra University Hospital, Coimbra, Portugal | [c] Faculty of Medicine and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal | [d] Memory and Dementia Center, Aristotle University, Thessaloniki, Greece | [e] Dokuz Eylul University, Department of Neurology and Brain Dynamics Center, Izmir, Turkey | [f] Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark | [g] Department of Neurology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece | [h] Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden | [i] Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

Correspondence: [*] Correspondence to: Alexandre de Mendonça, Department of Neurosciences and Pharmacology, Faculty of Medicine of the University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal. Tel.: +35 1217985183; Fax: +35 1217999454; [email protected]

Abstract: 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 Aβ 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±1.15μg/mL in the CSF and 1.20±1.88μg/mL in the plasma. No correlation was found between caffeine consumption and Aβ 42 in the CSF. However, a significant positive correlation was found between the concentrations of theobromine, both in the CSF and in the plasma, with Aβ 42 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.

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, caffeine, cerebrospinal fluid, metabolism, mild cognitive impairment, phosphotau, theobromine, total tau

DOI: 10.3233/JAD-150374

Journal: Journal of Alzheimer's Disease, vol. 47, no. 4, pp. 1069-1078, 2015