Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Detalhes bibliográficos
Autor(a) principal: Ramos de Matos, M
Data de Publicação: 2018
Outros Autores: Ferreira, C, Herukka, SK, Soininen, H, Janeiro, A, Santana, I, Baldeiras, I, Almeida, MR, Lleó, A, Dols-Icardo, O, Alcolea, D, Benussi, L, Binetti, G, Paterlini, A, Ghidoni, R, Nacmias, B, Meulenbroek, O, van Waalwijk van Doorn, LJ, Kuiperi, HJ, Hausner, L, Waldemar, G, Simonsen, AH, Tsolaki, M, Gkatzima, O, Resende de Oliveira, C, Verbeek, MM, Clarimon, J, Hiltunen, M, de Mendonça, A, Martins, M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.4/2255
Resumo: Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in the Alzheimer's disease (AD) field, and are now being applied in clinical practice. CSF amyloid-beta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect disease pathology, and may be used as quantitative traits for genetic analyses, fostering the identification of new genetic factors and the proposal of novel biological pathways of the disease. In patients, the concentration of CSF Aβ1-42 is decreased due to the accumulation of Aβ1-42 in amyloid plaques in the brain, while t-tau and p-tau levels are increased, indicating the extent of neuronal damage. To better understand the biological mechanisms underlying the regulation of AD biomarkers, and its relation to AD, we examined the association between 36 selected single nucleotide polymorphisms (SNPs) and AD biomarkers Aβ1-42, t-tau, and p-tau in CSF in a cohort of 672 samples (571 AD patients and 101 controls) collected within 10 European consortium centers.Our results highlighted five genes, APOE, LOC100129500, PVRL2, SNAR-I, and TOMM40, previously described as main players in the regulation of CSF biomarkers levels, further reinforcing a role for these in AD pathogenesis. Three new AD susceptibility loci, INPP5D, CD2AP, and CASS4, showed specific association with CSF tau biomarkers. The identification of genes that specifically influence tau biomarkers point out to mechanisms, independent of amyloid processing, but in turn related to tau biology that may open new venues to be explored for AD treatment.
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spelling Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid BiomarkersDoença de AlzheimerBiomarcadoresCerebrospinal fluid (CSF) biomarkers have been extensively investigated in the Alzheimer's disease (AD) field, and are now being applied in clinical practice. CSF amyloid-beta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect disease pathology, and may be used as quantitative traits for genetic analyses, fostering the identification of new genetic factors and the proposal of novel biological pathways of the disease. In patients, the concentration of CSF Aβ1-42 is decreased due to the accumulation of Aβ1-42 in amyloid plaques in the brain, while t-tau and p-tau levels are increased, indicating the extent of neuronal damage. To better understand the biological mechanisms underlying the regulation of AD biomarkers, and its relation to AD, we examined the association between 36 selected single nucleotide polymorphisms (SNPs) and AD biomarkers Aβ1-42, t-tau, and p-tau in CSF in a cohort of 672 samples (571 AD patients and 101 controls) collected within 10 European consortium centers.Our results highlighted five genes, APOE, LOC100129500, PVRL2, SNAR-I, and TOMM40, previously described as main players in the regulation of CSF biomarkers levels, further reinforcing a role for these in AD pathogenesis. Three new AD susceptibility loci, INPP5D, CD2AP, and CASS4, showed specific association with CSF tau biomarkers. The identification of genes that specifically influence tau biomarkers point out to mechanisms, independent of amyloid processing, but in turn related to tau biology that may open new venues to be explored for AD treatment.RIHUCRamos de Matos, MFerreira, CHerukka, SKSoininen, HJaneiro, ASantana, IBaldeiras, IAlmeida, MRLleó, ADols-Icardo, OAlcolea, DBenussi, LBinetti, GPaterlini, AGhidoni, RNacmias, BMeulenbroek, Ovan Waalwijk van Doorn, LJKuiperi, HJHausner, LWaldemar, GSimonsen, AHTsolaki, MGkatzima, OResende de Oliveira, CVerbeek, MMClarimon, JHiltunen, Mde Mendonça, AMartins, M2019-08-22T15:39:21Z20182018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.4/2255engJ Alzheimers Dis. 2018;66(2):639-652.10.3233/JAD-180512info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-11T14:23:38Zoai:rihuc.huc.min-saude.pt:10400.4/2255Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:04:43.410428Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
spellingShingle Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
Ramos de Matos, M
Doença de Alzheimer
Biomarcadores
title_short Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_full Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_fullStr Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_full_unstemmed Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
title_sort Quantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkers
author Ramos de Matos, M
author_facet Ramos de Matos, M
Ferreira, C
Herukka, SK
Soininen, H
Janeiro, A
Santana, I
Baldeiras, I
Almeida, MR
Lleó, A
Dols-Icardo, O
Alcolea, D
Benussi, L
Binetti, G
Paterlini, A
Ghidoni, R
Nacmias, B
Meulenbroek, O
van Waalwijk van Doorn, LJ
Kuiperi, HJ
Hausner, L
Waldemar, G
Simonsen, AH
Tsolaki, M
Gkatzima, O
Resende de Oliveira, C
Verbeek, MM
Clarimon, J
Hiltunen, M
de Mendonça, A
Martins, M
author_role author
author2 Ferreira, C
Herukka, SK
Soininen, H
Janeiro, A
Santana, I
Baldeiras, I
Almeida, MR
Lleó, A
Dols-Icardo, O
Alcolea, D
Benussi, L
Binetti, G
Paterlini, A
Ghidoni, R
Nacmias, B
Meulenbroek, O
van Waalwijk van Doorn, LJ
Kuiperi, HJ
Hausner, L
Waldemar, G
Simonsen, AH
Tsolaki, M
Gkatzima, O
Resende de Oliveira, C
Verbeek, MM
Clarimon, J
Hiltunen, M
de Mendonça, A
Martins, M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv RIHUC
dc.contributor.author.fl_str_mv Ramos de Matos, M
Ferreira, C
Herukka, SK
Soininen, H
Janeiro, A
Santana, I
Baldeiras, I
Almeida, MR
Lleó, A
Dols-Icardo, O
Alcolea, D
Benussi, L
Binetti, G
Paterlini, A
Ghidoni, R
Nacmias, B
Meulenbroek, O
van Waalwijk van Doorn, LJ
Kuiperi, HJ
Hausner, L
Waldemar, G
Simonsen, AH
Tsolaki, M
Gkatzima, O
Resende de Oliveira, C
Verbeek, MM
Clarimon, J
Hiltunen, M
de Mendonça, A
Martins, M
dc.subject.por.fl_str_mv Doença de Alzheimer
Biomarcadores
topic Doença de Alzheimer
Biomarcadores
description Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in the Alzheimer's disease (AD) field, and are now being applied in clinical practice. CSF amyloid-beta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect disease pathology, and may be used as quantitative traits for genetic analyses, fostering the identification of new genetic factors and the proposal of novel biological pathways of the disease. In patients, the concentration of CSF Aβ1-42 is decreased due to the accumulation of Aβ1-42 in amyloid plaques in the brain, while t-tau and p-tau levels are increased, indicating the extent of neuronal damage. To better understand the biological mechanisms underlying the regulation of AD biomarkers, and its relation to AD, we examined the association between 36 selected single nucleotide polymorphisms (SNPs) and AD biomarkers Aβ1-42, t-tau, and p-tau in CSF in a cohort of 672 samples (571 AD patients and 101 controls) collected within 10 European consortium centers.Our results highlighted five genes, APOE, LOC100129500, PVRL2, SNAR-I, and TOMM40, previously described as main players in the regulation of CSF biomarkers levels, further reinforcing a role for these in AD pathogenesis. Three new AD susceptibility loci, INPP5D, CD2AP, and CASS4, showed specific association with CSF tau biomarkers. The identification of genes that specifically influence tau biomarkers point out to mechanisms, independent of amyloid processing, but in turn related to tau biology that may open new venues to be explored for AD treatment.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-01-01T00:00:00Z
2019-08-22T15:39:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.4/2255
url http://hdl.handle.net/10400.4/2255
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Alzheimers Dis. 2018;66(2):639-652.
10.3233/JAD-180512
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eu_rights_str_mv openAccess
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dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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