Polymorphisms within serotonin receptor genes are associated with genetic, cerebrospinal fluid and neuropsychological biomarkers of Alzheimer’s disease

Decrease in serotonergic transmission throughout the brain is among the earliest pathological changes in Alzheimer’s disease (AD). Serotonergic receptors are also affected in AD. Polymorphisms in genes for serotonin (5HT) receptors were mostly associated with behavioral and psychological symptoms of dementia (BPSD). In this study we aimed to test if individuals carrying different genotypes in 5HTR1B rs13212041, 5HTR2A rs6313 (T102C), 5HTR2C rs3813929 (-795C/T) and 5HTR6 rs1805054 (C267T) polymorphisms have higher risk for development of AD. Study included 115 AD patients and 53 mild cognitive impairment patients with determined cerebrospinal fluid (CSF) AD biomarkers, neuropsychological tests, and apolipoprotein E (APOE) haplotype and 2701 cognitively healthy individuals with determined APOE haplotype. All four analysed polymorphisms of serotonin receptor genes showed the association with either genetic, CSF or neuropsychological biomarkers of AD. Thus, these polymorphisms deserve further investigation as potential genetic biomarkers and therapeutic targets for AD.