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• W2102663886 abstract "Butyrylcholinesterase K (BCHE-K) is associated with increased risk of developing Alzheimer's disease (AD) in apolipoprotein ε (APOE4) carriers, while among APOE4 non-carriers BCHE-K appears to be protective. Nonetheless, pure pharmacogenetic reports have provided conflicting results. To provide insights about these controversies, we combined BCHE-K pharmacogenetic observations in AD patients (n = 179) with proteomic and enzymatic analysis of plasma, cerebrospinal fluid (CSF), or both samples. We found that BCHE-K genotype was overrepresented among the AD patients (χ(2) = 14.21, p < 0.0001). Plasma BuChE activity was gene dose-dependently 20-50% less among K-carriers (p < 0.001). CSF BuChE activity did not show such robust K-gene dosage-dependency, because K homozygotes (n = 9) had 30-40% less activity compared to both non-carriers (n = 78, p < 0.01) and heterozygotes (n = 42, p < 0.09). CSF ApoE protein expression was also altered by presence of K-allele (p < 0.001, n = 129). Mutually, APOE4 altered phenotypic display of BuChE variants in CSF (p < 0.01, n = 129). In absence of APOE4, CSF BuChE activity was essentially indistinguishable among K-carriers (n = 16) and non-carriers (n = 17, p < 0.8) although the K-carriers had 24-39% less circulating BuChE protein. In contrast in presence of APOE4, the K-carriers (n = 35) had K allele dose-dependently a BuChE phenotype with 14-46% reduced activity compared to K non-carriers (p < 0.001, n = 59), despite an essentially identical BChE concentration in CSF (1 ± 4%, p < 0.8). Pattern of the patients' cognitive performance in MMSE closely resembled the APOE4-derived phenotypic display of BuChE variants. APOE4-dependent outcome of BCHE-K genotype as AD risk factor arises through a differential phenotypic modulation of BuChE. Future pharmacogenetic studies should include assessment of the subjects' true phenotypic display of BuChE." @default.
• W2102663886 created "2016-06-24" @default.
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• W2102663886 date "2012-01-25" @default.
• W2102663886 modified "2023-10-03" @default.
• W2102663886 title "Apolipoprotein ε4 Modulates Phenotype of Butyrylcholinesterase in CSF of Patients with Alzheimer's Disease" @default.
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• W2102663886 doi "https://doi.org/10.3233/jad-2011-111088" @default.
• W2102663886 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22012848" @default.
• W2102663886 hasPublicationYear "2012" @default.
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