Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease

Serotonin or 5-hydroxytryptamine (5-HT) is primarily involved in the regulation of learning and memory. Pathological changes in metabolism or functional imbalance of 5-HT has been associated with Alzheimer's disease (AD). The hypothesis tested is that in peripheral blood, markers of the serotonergic pathway can be used as a diagnostic tool for AD. The current study measured the relative expression of 5-HT receptors (5-HTR2A and 5-HTR3A) as well as the 5-HT catalytic enzyme, Monoamine oxidase A (MAO-A) mRNA in Peripheral Blood Mononuclear Cells (PBMCs) of patients with late-onset Alzheimer's disease (LOAD) and age-matched controls. 5-HTR2A, 5-HTR3A, and MAO-A mRNA expressions were examined in PBMCs of 30 patients with LOAD and 30 control individuals. Real-time quantitative PCR was used to measure mRNA expression. The dementia status of patients in this study was assessed using a Mini-Mental State Examination (MMSE). Mean data of relative mRNA expression of 5-HTR2A, 5-HTR3A and MAO-A were significantly lower in PBMCs of patients with LOAD compared with controls. Based on the down-regulation of serotonergic markers in PBMCs, our findings may be another claim to the systemic nature of LOAD. The role of peripheral serotonergic downregulation, in the pathogenesis of AD, needs to be further studied. Given the extremely convenient access to PBMCs, these molecular events may represent more complete dimensions of AD neuropathophysiology or possibly lead to a new direction in studies focused on blood-based markers.