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

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 sympt...

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Autores principales: Babić Leko, Mirjana, Nikolac Perković, Matea, Španić, Ena, Švob Štrac, Dubravka, Pleić, Nikolina, Vogrinc, Željka, Gunjača, Ivana, Bežovan, Dora, Nedić Erjavec, Gordana, Klepac, Nataša, Borovečki, Fran, Zemunik, Tatijana, Pivac, Nela, Hof, Patrick R., Šimić, Goran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775360/
https://www.ncbi.nlm.nih.gov/pubmed/36551873
http://dx.doi.org/10.3390/biomedicines10123118
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author Babić Leko, Mirjana
Nikolac Perković, Matea
Španić, Ena
Švob Štrac, Dubravka
Pleić, Nikolina
Vogrinc, Željka
Gunjača, Ivana
Bežovan, Dora
Nedić Erjavec, Gordana
Klepac, Nataša
Borovečki, Fran
Zemunik, Tatijana
Pivac, Nela
Hof, Patrick R.
Šimić, Goran
author_facet Babić Leko, Mirjana
Nikolac Perković, Matea
Španić, Ena
Švob Štrac, Dubravka
Pleić, Nikolina
Vogrinc, Željka
Gunjača, Ivana
Bežovan, Dora
Nedić Erjavec, Gordana
Klepac, Nataša
Borovečki, Fran
Zemunik, Tatijana
Pivac, Nela
Hof, Patrick R.
Šimić, Goran
author_sort Babić Leko, Mirjana
collection PubMed
description 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 β(1–42) (Aβ(1–42)) and an increase in p-tau(181)/Aβ(1–42) 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.
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spelling pubmed-97753602022-12-23 Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease Babić Leko, Mirjana Nikolac Perković, Matea Španić, Ena Švob Štrac, Dubravka Pleić, Nikolina Vogrinc, Željka Gunjača, Ivana Bežovan, Dora Nedić Erjavec, Gordana Klepac, Nataša Borovečki, Fran Zemunik, Tatijana Pivac, Nela Hof, Patrick R. Šimić, Goran Biomedicines Article 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 β(1–42) (Aβ(1–42)) and an increase in p-tau(181)/Aβ(1–42) 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. MDPI 2022-12-02 /pmc/articles/PMC9775360/ /pubmed/36551873 http://dx.doi.org/10.3390/biomedicines10123118 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Babić Leko, Mirjana
Nikolac Perković, Matea
Španić, Ena
Švob Štrac, Dubravka
Pleić, Nikolina
Vogrinc, Željka
Gunjača, Ivana
Bežovan, Dora
Nedić Erjavec, Gordana
Klepac, Nataša
Borovečki, Fran
Zemunik, Tatijana
Pivac, Nela
Hof, Patrick R.
Šimić, Goran
Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title_full Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title_fullStr Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title_full_unstemmed Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title_short Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease
title_sort serotonin receptor gene polymorphisms are associated with cerebrospinal fluid, genetic, and neuropsychological biomarkers of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775360/
https://www.ncbi.nlm.nih.gov/pubmed/36551873
http://dx.doi.org/10.3390/biomedicines10123118
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