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Cerebrospinal fluid amyloid-beta 1–42 (Aβ 1–42 ) and phosphorylated Tau at position 181 (pTau 181 ) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ 1–42  and pTau 181  in AD dementia patients followed by independent replication. An association was found between Aβ 1–42  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 Aβ 1–42 .

SUCLG2 identified as both a determinator of CSF Aβ 1–42 levels and an attenuator of cognitive decline in Alzheimer's disease