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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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/12/3118 |
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| author | Mirjana Babić Leko Matea Nikolac Perković Ena Španić Dubravka Švob Štrac Nikolina Pleić Željka Vogrinc Ivana Gunjača Dora Bežovan Gordana Nedić Erjavec Nataša Klepac Fran Borovečki Tatijana Zemunik Nela Pivac Patrick R. Hof Goran Šimić |
| author_facet | Mirjana Babić Leko Matea Nikolac Perković Ena Španić Dubravka Švob Štrac Nikolina Pleić Željka Vogrinc Ivana Gunjača Dora Bežovan Gordana Nedić Erjavec Nataša Klepac Fran Borovečki Tatijana Zemunik Nela Pivac Patrick R. Hof Goran Šimić |
| author_sort | Mirjana Babić Leko |
| collection | DOAJ |
| 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 <i>5HTR1B</i> rs13212041, <i>5HTR2A</i> rs6313 (T102C), <i>5HTR2C</i> rs3813929 (−759C/T), and <i>5HTR6</i> 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 (<i>APOE</i>) 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<sub>1–42</sub> (Aβ<sub>1–42</sub>) and an increase in p-tau<sub>181</sub>/Aβ<sub>1–42</sub> ratio in carriers of the T allele in the <i>5HTR2C</i> rs3813929 (−759C/T) polymorphism. A significantly higher number of <i>APOE</i> ε4 allele carriers was observed among individuals carrying a TT genotype within the <i>5HTR2A</i> T102C polymorphism, a C allele within the <i>5HTR1B</i> rs13212041 polymorphism, and a T allele within the <i>5HTR6</i> rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the <i>5HTR1B</i> 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 <i>5HTR6</i> 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. |
| first_indexed | 2024-03-09T17:18:00Z |
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| last_indexed | 2024-03-09T17:18:00Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-313b3714eecd4961a99c3c81f56df4f52023-11-24T13:27:06ZengMDPI AGBiomedicines2227-90592022-12-011012311810.3390/biomedicines10123118Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s DiseaseMirjana Babić Leko0Matea Nikolac Perković1Ena Španić2Dubravka Švob Štrac3Nikolina Pleić4Željka Vogrinc5Ivana Gunjača6Dora Bežovan7Gordana Nedić Erjavec8Nataša Klepac9Fran Borovečki10Tatijana Zemunik11Nela Pivac12Patrick R. Hof13Goran Šimić14Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, 10000 Zagreb, CroatiaDepartment of Molecular Medicine, Institute Ruđer Bošković, 10000 Zagreb, CroatiaDepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, 10000 Zagreb, CroatiaDepartment of Molecular Medicine, Institute Ruđer Bošković, 10000 Zagreb, CroatiaDepartment of Medical Biology, School of Medicine, University of Split, 21000 Split, CroatiaLaboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDepartment of Medical Biology, School of Medicine, University of Split, 21000 Split, CroatiaGeneral Hospital Zabok, 49210 Zabok, CroatiaDepartment of Molecular Medicine, Institute Ruđer Bošković, 10000 Zagreb, CroatiaDepartment of Neurology, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDepartment of Neurology, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDepartment of Medical Biology, School of Medicine, University of Split, 21000 Split, CroatiaDepartment of Molecular Medicine, Institute Ruđer Bošković, 10000 Zagreb, CroatiaNash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, 10000 Zagreb, CroatiaA 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 <i>5HTR1B</i> rs13212041, <i>5HTR2A</i> rs6313 (T102C), <i>5HTR2C</i> rs3813929 (−759C/T), and <i>5HTR6</i> 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 (<i>APOE</i>) 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<sub>1–42</sub> (Aβ<sub>1–42</sub>) and an increase in p-tau<sub>181</sub>/Aβ<sub>1–42</sub> ratio in carriers of the T allele in the <i>5HTR2C</i> rs3813929 (−759C/T) polymorphism. A significantly higher number of <i>APOE</i> ε4 allele carriers was observed among individuals carrying a TT genotype within the <i>5HTR2A</i> T102C polymorphism, a C allele within the <i>5HTR1B</i> rs13212041 polymorphism, and a T allele within the <i>5HTR6</i> rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the <i>5HTR1B</i> 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 <i>5HTR6</i> 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.https://www.mdpi.com/2227-9059/10/12/3118Alzheimer’s disease5-hydroxytryptamine (serotonin)5HT receptorsbiomarkerscerebrospinal fluidMini-Mental State Examination |
| spellingShingle | Mirjana Babić Leko Matea Nikolac Perković Ena Španić Dubravka Švob Štrac Nikolina Pleić Željka Vogrinc Ivana Gunjača Dora Bežovan Gordana Nedić Erjavec Nataša Klepac Fran Borovečki Tatijana Zemunik Nela Pivac Patrick R. Hof Goran Šimić Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer’s Disease Biomedicines Alzheimer’s disease 5-hydroxytryptamine (serotonin) 5HT receptors biomarkers cerebrospinal fluid Mini-Mental State Examination |
| 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 | Alzheimer’s disease 5-hydroxytryptamine (serotonin) 5HT receptors biomarkers cerebrospinal fluid Mini-Mental State Examination |
| url | https://www.mdpi.com/2227-9059/10/12/3118 |
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