title: Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?
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 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.
authors.affiliation: Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Travassos
authors.affiliation: Department of Neurology, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: Faculty of Medicine and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Baldeiras
authors.affiliation: Memory and Dementia Center, Aristotle University, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Memory and Dementia Center, Aristotle University, Thessaloniki, Greece.
authors.forename: Olymbia
authors.initials: O
authors.lastname: Gkatzima
authors.affiliation: Dokuz Eylul University, Department of Neurology and Brain Dynamics Center, Izmir, Turkey.
authors.forename: Genc
authors.initials: G
authors.lastname: Sermin
authors.affiliation: Dokuz Eylul University, Department of Neurology and Brain Dynamics Center, Izmir, Turkey.
authors.forename: Görsev G
authors.initials: GG
authors.lastname: Yener
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Anja
authors.initials: A
authors.lastname: Simonsen
authors.affiliation: Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
authors.affiliation: Department of Neurology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kapaki
authors.affiliation: Department of Neurology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Bourbouli
authors.initials: B
authors.lastname: Mara
authors.affiliation: Faculty of Medicine and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Faculty of Medicine and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Agostinho
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Mendes
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Manadas
authors.affiliation: Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Alexandreça
authors.initials: A
authors.lastname: de Mendon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013805:Theobromine / Q000097:blood / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D016875:tau Proteins; D002110:Caffeine; D013805:Theobromine
keywords: Alzheimer’s disease; amyloid-β; biomarkers; caffeine; cerebrospinal fluid; metabolism; mild cognitive impairment; phosphotau; theobromine; total tau