en
Scientific article
English

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease

CollaboratorsPopp, Julius
Published inHuman Molecular Genetics, vol. 23, no. 24, p. 6644-6658
Publication date2014
Abstract

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

Keywords
  • Aged
  • Alzheimer Disease/cerebrospinal fluid/genetics/pathology
  • Amyloid beta-Peptides/cerebrospinal fluid/genetics
  • Apolipoprotein E4/cerebrospinal fluid/genetics
  • Cognition
  • Female
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Humans
  • Male
  • Nuclear Proteins/cerebrospinal fluid/genetics
  • Peptide Fragments/cerebrospinal fluid/genetics
  • Phosphorylation
  • Polymorphism
  • Single Nucleotide
  • RNA-Binding Proteins/cerebrospinal fluid/genetics
  • Serine-Arginine Splicing Factors
  • Signal Transduction
  • tau Proteins/cerebrospinal fluid/genetics
Affiliation Not a UNIGE publication
Citation (ISO format)
RAMIREZ, Alfredo et al. SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer’s disease. In: Human Molecular Genetics, 2014, vol. 23, n° 24, p. 6644–6658. doi: 10.1093/hmg/ddu372
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0964-6906
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