Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease

Scientific paper - Original scientific paper

• Author: Mirjana Babić Leko
• Author: Matea Nikolac Perković
• Author: Ena Španić
• Author: Dubravka Švob Štrac
• Author: Nikolina Pleić
• Author: Željka Vogrinc
• Author: Ivana Gunjača
• Author: Dora Bežovan
• Author: Gordana Nedić Erjavec
• Author: Nataša Klepac
• Author: Fran Borovečki
• Author: Tatijana Zemunik
• Author: Nela Pivac
• Author: Patrick R. Hof
• Author: Goran Šimić
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Neurology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience

Abstract (english)

A 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 of serotonin (5HT) receptors have been mostly associated with behavioral and psychological symptoms of dementia (BPSD). In this study, we examined if AD patients carrying different genotypes in 5HTR1B rs13212041, 5HTR2A rs6313 (T102C), 5HTR2C rs3813929 (−759C/T), and 5HTR6 rs1805054 (C267T) polymorphisms have a higher risk of faster disease progression (assessed by neuropsychological testing), are more prone to develop AD-related pathology (reflected by levels of cerebrospinal fluid [CSF] AD biomarkers), or have an association with an apolipoprotein E (APOE) haplotype. This study included 115 patients with AD, 53 patients with mild cognitive impairment (MCI), and 2701 healthy controls. AD biomarkers were determined in the CSF of AD and MCI patients using enzyme-linked immunosorbent assays (ELISA), while polymorphisms were determined using either TaqMan SNP Genotyping Assays or Illumina genotyping platforms. We detected a significant decrease in the CSF amyloid β1–42 (Aβ1–42) and an increase in p-tau181/Aβ1–42 ratio in carriers of the T allele in the 5HTR2C rs3813929 (−759C/T) polymorphism. A significantly higher number of APOE ε4 allele carriers was observed among individuals carrying a TT genotype within the 5HTR2A T102C polymorphism, a C allele within the 5HTR1B rs13212041 polymorphism, and a T allele within the 5HTR6 rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the 5HTR1B rs13212041 polymorphism were significantly more represented among AD patients and had poorer performances on the Rey–Osterrieth test. Carriers of the T allele within the 5HTR6 rs1805054 had poorer performances on the MMSE and ADAS–Cog. As all four analyzed polymorphisms of serotonin receptor genes showed an association with either genetic, CSF, or neuropsychological biomarkers of AD, they deserve further investigation as potential early genetic biomarkers of AD.

• Keywords (english): 5-hydroxytryptamine (serotonin); 5HT receptors; Alzheimer’s disease; Mini-Mental State Examination; apolipoprotein E; biomarkers; cerebrospinal fluid
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Biomedicines
• Numbering: vol. 10, no. 12, 3118
• e-ISSN: 2227-9059
• DOI: https://doi.org/10.3390/biomedicines10123118
• URN:NBN: urn:nbn:hr:105:453653
• Publication: 2022-12-02
• Project: Number: IP-2019-04-3584; Title (croatian): Uloga krvno-moždane barijere, urođene imunosti i oligomerizacije tau proteina u patogenezi Alzheimerove bolesti; Title (english): Role of blood-brain barrier, innate immunity, and tau protein oligomerization in the pathogenesis of Alzheimer's disease; Acronym: ALZ-BBB-INNATETAU; Leader: Goran Šimić; Jurisdiction: Croatia; Funding stream: IP
• Project: Number: IP-2014-09-9730; Title (croatian): Hiperfosforilacija, agregacija i transsinaptički prijenos tau proteina u Alzheimerovoj bolesti: analiza likvora i ispitivanje potencijalnih neuroprotektivnih spojeva; Title (english): Tau protein hyperphosphorylation, aggregation and trans-synaptic transfer in Alzheimer's disease: cerebrospinal fluid analysis and assessment of potential neuroprotective compounds; Acronym: ALZTAUPROTECT; Jurisdiction: Croatia; Funding stream: IP
• Project: Number: IP-2019-04-2593; Title (croatian): Reguliranje funkcije štitne i doštitne žlijezde i homeostaze kalcija u krvi; Title (english): Regulation of thyroid and parathyroid function and blood calcium homeostasis; Acronym: THPTHCAREGULATION; Leader: Tatijana Zemunik; Jurisdiction: Croatia; Funding stream: IP
• Document URL: https://www.mdpi.com/2227-9059/10/12/3118
• Type of resource: Text
• Access conditions: Open access
• Created on: 2023-05-15 10:42:16