SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease
Copyright policy )SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease
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.
- University of Bonn Germany
- University of Mary United States
- Vrije Universiteit Amsterdam Netherlands
- Amsterdam UMC Netherlands
- University of Lille France
Male, cerebrospinal fluid [Apolipoprotein E4], Apolipoprotein E4, cerebrospinal fluid [Nuclear Proteins], genetics [Alzheimer Disease], cerebrospinal fluid [Amyloid beta-Peptides], pathology [Alzheimer Disease], Cognition, genetics [Amyloid beta-Peptides], genetics [RNA-Binding Proteins], Phosphorylation, genetics [Apolipoprotein E4], Serine-Arginine Splicing Factors, Nuclear Proteins, RNA-Binding Proteins, genetics [Nuclear Proteins], Single Nucleotide, amyloid beta-protein (1-42), cerebrospinal fluid [Alzheimer Disease], Female, Signal Transduction, RNA-Binding Proteins/cerebrospinal fluid/genetics, 610, tau Proteins, Polymorphism, Single Nucleotide, Alzheimer Disease, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Humans, cerebrospinal fluid [Peptide Fragments], cerebrospinal fluid [RNA-Binding Proteins], Polymorphism, Aged, tau Proteins/cerebrospinal fluid/genetics, Amyloid beta-Peptides, Apolipoprotein E4/cerebrospinal fluid/genetics, Nuclear Proteins/cerebrospinal fluid/genetics, genetics [Peptide Fragments], Peptide Fragments, Amyloid beta-Peptides/cerebrospinal fluid/genetics, genetics [tau Proteins], cerebrospinal fluid [tau Proteins], Gene Expression Regulation, Alzheimer Disease/cerebrospinal fluid/genetics/pathology, Peptide Fragments/cerebrospinal fluid/genetics, Genome-Wide Association Study, ddc: ddc:570
Male, cerebrospinal fluid [Apolipoprotein E4], Apolipoprotein E4, cerebrospinal fluid [Nuclear Proteins], genetics [Alzheimer Disease], cerebrospinal fluid [Amyloid beta-Peptides], pathology [Alzheimer Disease], Cognition, genetics [Amyloid beta-Peptides], genetics [RNA-Binding Proteins], Phosphorylation, genetics [Apolipoprotein E4], Serine-Arginine Splicing Factors, Nuclear Proteins, RNA-Binding Proteins, genetics [Nuclear Proteins], Single Nucleotide, amyloid beta-protein (1-42), cerebrospinal fluid [Alzheimer Disease], Female, Signal Transduction, RNA-Binding Proteins/cerebrospinal fluid/genetics, 610, tau Proteins, Polymorphism, Single Nucleotide, Alzheimer Disease, DDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit, Humans, cerebrospinal fluid [Peptide Fragments], cerebrospinal fluid [RNA-Binding Proteins], Polymorphism, Aged, tau Proteins/cerebrospinal fluid/genetics, Amyloid beta-Peptides, Apolipoprotein E4/cerebrospinal fluid/genetics, Nuclear Proteins/cerebrospinal fluid/genetics, genetics [Peptide Fragments], Peptide Fragments, Amyloid beta-Peptides/cerebrospinal fluid/genetics, genetics [tau Proteins], cerebrospinal fluid [tau Proteins], Gene Expression Regulation, Alzheimer Disease/cerebrospinal fluid/genetics/pathology, Peptide Fragments/cerebrospinal fluid/genetics, Genome-Wide Association Study, ddc: ddc:570
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