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

2018Journal article Open access
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dc.contributor.authorRamos de Matos, M
dc.contributor.authorFerreira, C
dc.contributor.authorHerukka, SK
dc.contributor.authorSoininen, H
dc.contributor.authorJaneiro, A
dc.contributor.authorSantana, I
dc.contributor.authorBaldeiras, I
dc.contributor.authorAlmeida, MR
dc.contributor.authorLleó, A
dc.contributor.authorDols-Icardo, O
dc.contributor.authorAlcolea, D
dc.contributor.authorBenussi, L
dc.contributor.authorBinetti, G
dc.contributor.authorPaterlini, A
dc.contributor.authorGhidoni, R
dc.contributor.authorNacmias, B
dc.contributor.authorMeulenbroek, O
dc.contributor.authorvan Waalwijk van Doorn, LJ
dc.contributor.authorKuiperi, HJ
dc.contributor.authorHausner, L
dc.contributor.authorWaldemar, G
dc.contributor.authorSimonsen, AH
dc.contributor.authorTsolaki, M
dc.contributor.authorGkatzima, O
dc.contributor.authorResende de Oliveira, C
dc.contributor.authorVerbeek, MM
dc.contributor.authorClarimon, J
dc.contributor.authorHiltunen, M
dc.contributor.authorde Mendonça, A
dc.contributor.authorMartins, M
dc.date.accessioned2019-08-22T15:39:21Z
dc.date.available2019-08-22T15:39:21Z
dc.date.issued2018
dc.description.abstractCerebrospinal 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Alzheimers Dis. 2018;66(2):639-652.pt_PT
dc.identifier.doi10.3233/JAD-180512pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.4/2255
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectDoença de Alzheimerpt_PT
dc.subjectBiomarcadorespt_PT
dc.titleQuantitative Genetics Validates Previous Genetic Variants and Identifies Novel Genetic Players Influencing Alzheimer's Disease Cerebrospinal Fluid Biomarkerspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage652pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage639-652pt_PT
oaire.citation.volume66pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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