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P1‐363: A blood‐based gene expression test for Alzheimer's disease identifies likelihood of progression in mild cognitive impairment patients
Author(s) -
Rye Philip,
Lönneborg Anders,
Sæbø Solve,
Wetterberg Peter,
Sharma Praveen,
Jensen Marianne,
Bårdsen Ken
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.945
Subject(s) - medicine , grading (engineering) , analysis of variance , oncology , disease , blood test , cognitive impairment , alzheimer's disease , biology , ecology
Background: Identifying biomarkers that can predict Alzheimer disease (AD) risk will be critical to early intervention and, ultimately, effective prevention. Plasma levels of circulating amyloid-beta (A ) 40 and 42 are attractive candidate biomarkers. However, reliability and other key properties of the assay must be established. Methods: Several U.S. laboratories involved in research on plasma A participated. Using five different protocols, blinded samples were assayed for concentrations of plasma A 40 and 42 in order to assess: intra-assay reliability; impact of using EDTA vs. heparin tubes on absolute A concentrations and on intra-assay reliability; percent recovery of known A concentrations in spiked samples; and effect of blood processing delays on measured A concentrations. Results: Median intra-assay coefficients of variation (CVs) for the different protocols ranged from 6-24% for A -40, and 8-14% for A -42. There were no differences in average A concentrations or intra-assay CVs by collection method (EDTA vs. heparin anticoagulant). Although reproducibility was generally good within each protocol, there was considerable variation in reported A concentrations across the protocols. In addition, percent recovery of expected concentrations was modest, ranging from -24% to 44% for A -40, and 17% to 61% for A -42. Finally, plasma concentrations of A species (particularly A -42) appeared stable in whole blood kept in ice packs and processed as long as 24 hours after collection; under one protocol, intra-class correlations of A -40 and A -42 concentrations were 0.95 after processing delays of 48 hours. Conclusions: Reproducibility of plasma A -40 and A -42 concentrations was generally good within each of 5 different assay protocols and was unaffected by differences in anticoagulants commonly used in blood collection. However, reported A concentrations varied considerably across protocols, and the percent recovery of known concentrations was modest; thus, comparisons of absolute plasma A concentrations across studies is probably of little value at this time. In addition, these results show that it is possible to attain stability of plasma A concentrations after processing delays that are typical of those occurring in many large population-based studies. Overall, these preliminary findings suggest that measurement of plasma A -40 and A -42 may be feasible in a variety of research settings.