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J Neurol. 2014 Jun;261(6):1187-95. doi: 10.1007/s00415-014-7335-6. Epub 2014 Apr 12.

The screening of Alzheimer's patients with CSF biomarkers, modulates the distribution of APOE genotype: impact on clinical trials.

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  • 1Memory Clinical Center CMRR Paris Nord Ile-de-France, Saint Louis-Lariboisiere, Fernand Widal Hospital, AP-HP, University Paris 7-Denis Diderot, Paris, France,


Polymorphism of the apolipoprotein E gene (APOE) plays a role in the level of neuropathological lesions and in drug response in Alzheimer's disease (AD). The aim of this study was to investigate whether the selection of AD patients based on cerebrospinal fluid (CSF) biomarkers assessment may be biased by their APOE distribution. We studied the relationships between APOE genotype and CSF biomarkers levels in a total of 432 patients (AD, n = 244; non-AD, n = 188) explored for cognitive disorders. We studied the distribution of APOE genotypes among AD patient subgroups selected by various cut-offs of CSF biomarkers. Strategies of screening based on CSF Aβ1-42 lead to overselection of ε4/ε4 patients in the AD group. Screening based on tau levels did not change Apoe4 distribution in the AD group. CSF Aβ1-42 discriminated better AD patients with at least one ε4 than AD patients with no ε4. A strong allele-effect relationship was detected between APOE genotype and CSF amyloid-β (Aβ1-42) in AD patients. Selecting AD patients on CSF amyloid levels only may create an overselection of ε4/ε4 carriers, and might potentially bias the population of patients included in clinical trial studies.

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