Association between low vitamin D status, serotonin and clinico-bio-behavioral parameters in Alzheimer's disease

Background: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients and on the potential association with cognition, and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with cognitive/BPSD scorings, serum serotonin (5-hydroxytryptamine, 5-HT) and cerebrospinal fluid (CSF) biomarker levels. Methods: Frozen serum samples of 25 well-characterized AD subjects were analyzed, of which 15 had a neuropathologically-confirmed diagnosis. Serum 25(OH)D3 levels were analyzed by means of LC-MS/MS, whereas 5-HT concentrations were quantified by competitive ELISA. Results: Among AD patients, vitamin D deficiency was highly prevalent, defined as levels below 50 nmol/L. Regression analyses, adjusted for age, gender and psychotropic medications, revealed that serum 25(OH)D3 and 5-HT were positively associated (p=0.012). Furthermore, serum 25(OH)D3 concentrations correlated inversely with CSF amyloid-beta (A beta 1-42) levels (p=0.006), and, serum 5-HT levels correlated positively with aggressiveness (p=0.001), frontal behavior (p=0.001), depression (p=0.004) and cognitive performance (p<0.005). Lastly, AD patients on cholinesterase inhibitors had higher serum 25(OH)D3 (p=0.030) and lower serum 5-HT (p=0.012) levels. Conclusions: The molecular associations between low vitamin D status, serum 5-HT and CSF A beta 1-42 levels are highly remarkable, warranting further mechanistic and intervention studies to disclose potential involvement in the clinico-bio-behavioral pathophysiology of AD.