Clin Chem Lab Med. 2026 Mar 16. doi: 10.1515/cclm-2026-0032. Online ahead of print.
ABSTRACT
OBJECTIVES: Since apolipoprotein E4 (ApoE4) is associated with therapy-related adverse effects of anti-amyloid-β monoclonal antibodies in Alzheimer’s disease, such as amyloid-related imaging abnormalities, methods for determining the ApoE4 status are needed. The Lumipulse® ApoE4 and Pan-ApoE assays provide a practical approach, but they have so far been validated only in plasma.
METHODS: Plasma and serum obtained from a single blood draw from 157 patients were analyzed using ApoE4 and Pan-ApoE chemiluminescent enzyme immunoassays. The APOE genotype was determined by allele-specific quantitative polymerase chain reaction. Additional experiments assessed assay repeatability, intermediate precision, and sample stability under various storage conditions.
RESULTS: ApoE4, Pan-ApoE, and the resulting ApoE4/Pan-ApoE ratio showed minimal bias, strong positive correlation and linearity between plasma and serum. Using matrix-specific thresholds, plasma- and serum-derived ApoE4/Pan-ApoE ratios accurately classified the ApoE4 phenotypes in concordance with APOE ε4 genotypes. The assay demonstrated repeatability of <15 % and <5 % (day 1 and 2), with intermediate precision <10 % for both Pan-ApoE and ApoE4. Plasma and serum showed both comparable stability after multiple freeze-thaw-cycles and up to 120 h at 4 °C, while serum showed deterioration after 120 h storage at 20 °C.
CONCLUSIONS: Using matrix-specific thresholds, the ApoE4/Pan-ApoE ratio in plasma and serum accurately classified the ApoE4 phenotype in concordance with APOE ε4 genotypes. Serum and plasma showed comparable stability and precision. Thus, serum is a reliable alternative to plasma for measuring Pan-ApoE and ApoE4 with the Lumipulse assays. The use of serum expands sample availability, particularly in retrospective studies or when collected alongside cerebrospinal fluid.
PMID:41842840 | DOI:10.1515/cclm-2026-0032