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.

Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage

“…As caffeine is rapidly metabolized to theophylline and paraxanthine (the main metabolites in rodents within 120 min 14 ), it is possible that these metabolites may also contribute to neuroprotection, as described for paraxanthine in models of Parkinson’s disease 48 , 49 and theobromine in models of Alzheimer’s disease. 50 …”

Health benefits of methylxanthines in neurodegenerative diseases

“…More recently, the findings of the Italian longitudinal study on aging have come out and confirm that sustained and moderate coffee consumption results in a reduced rate of the incidence of mild cognitive impairment . An estimate of caffeine levels in AD patients taking caffeine‐containing beverages has been recently provided; they were reported to be approximately 1 μg/mL (0.79 μg/mL in the cerebrospinal fluid and 1.20 in plasma) .…”

“…Although caffeine levels do not correlate with the level of potential biomarkers for AD, for instance with the level of amyloid peptide β 1‐42 (Aβ 1‐42 ) in the cerebrospinal fluid of patients, this correlation occurs in the case of theobromine . The authors of the study suggested that theobromine may have a neuroprotective role in amyloid‐mediated neurotoxicity.…”

Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline

“…Because of this, the consumption of cocoarelated products exposes humans both to theobromine from the demethylation of caffeine, in addition to the direct ingestion of theobromine contained in these products [33]. Remarkably, a recent study showed a significant positive correlation between the concentrations of theobromine in the cerebrospinal fluid (CSF) and in the plasma with the AD CSF biomarker A␤ 42 , suggesting that theobromine is associated with a healthier CSF biomarker profile and eventually may have a protective effect against the development of AD [44]. The observation that the protective effect of chocolate consumption on cognitive decline was observed only among subjects with low daily consumption of caffeine may suggest that caffeine is not the relevant component involved in this protective effect.…”