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

Mafalda Ramos de Matos | Zendy; Catarina B. Ferreira | Zendy; Sanna-Kaisa Herukka | Zendy; Hilkka Soininen | Zendy; André Janeiro | Zendy; Isabel Santana | Zendy; Inês Baldeiras | Zendy; Maria Rosário Almeida | Zendy; Alberto Lleó | Zendy; Oriol DolsIcardo | Zendy; Daniel Alcolea | Zendy; Luisa Benussi | Zendy; Giuliano Binetti | Zendy; Anna Paterlini | Zendy; Roberta Ghidoni | Zendy; Benedetta Nacmias | Zendy; Olga Meulenbroek | Zendy; Linda J.C. van Waalwijk van Doorn | Zendy; H. Bea j Kuiperi | Zendy; Lucrezia Hausner | Zendy; Gunhild Waldemar | Zendy; Anja Hviid Simonsen | Zendy; Magda Tsolaki | Zendy; Olymbia Gkatzima | Zendy; Catarina R. Oliveira | Zendy; Marcel M. Verbeek | Zendy; Jordi Clarimón | Zendy; Mikko Hiltunen | Zendy; Alexandre de Mendonça | Zendy; Madalena Martins | Zendy

Open Access

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

Author(s) -

Mafalda Ramos de Matos,

Catarina B. Ferreira,

Sanna-Kaisa Herukka,

Hilkka Soininen,

André Janeiro,

Isabel Santana,

Inês Baldeiras,

Maria Rosário Almeida,

Alberto Lleó,

Oriol DolsIcardo,

Daniel Alcolea,

Luisa Benussi,

Giuliano Binetti,

Anna Paterlini,

Roberta Ghidoni,

Benedetta Nacmias,

Olga Meulenbroek,

Linda J.C. van Waalwijk van Doorn,

H. Bea j Kuiperi,

Lucrezia Hausner,

Gunhild Waldemar,

Anja Hviid Simonsen,

Magda Tsolaki,

Olymbia Gkatzima,

Catarina R. Oliveira,

Marcel M. Verbeek,

Jordi Clarimón,

Mikko Hiltunen,

Alexandre de Mendonça,

Madalena Martins

Publication year - 2018

Publication title -

journal of alzheimer s disease

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.677

H-Index - 139

eISSN - 1875-8908

pISSN - 1387-2877

DOI - 10.3233/jad-180512

Subject(s) - cerebrospinal fluid , single nucleotide polymorphism , apolipoprotein e , disease , pathogenesis , amyloid beta , alzheimer's disease , biology , tau protein , genetic association , genetics , bioinformatics , gene , medicine , genotype , neuroscience , pathology , immunology

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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