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O1‐03‐01: In‐depth molecular genetic analysis of CLU in Alzheimer's disease
Author(s) -
Bettens Karolien,
Brouwers Nathalie,
Gil Ana,
Van Miegroet Helen,
Engelborghs Sebastiaan,
De Deyn Peter P.,
Vandenberghe Rik,
Sleegers Kristel,
Van Broeckhoven Christine
Publication year - 2010
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.2010.05.217
Subject(s) - clusterin , genetics , biology , single nucleotide polymorphism , genome wide association study , genetic association , locus (genetics) , genotype , genetic variation , haplotype , gene , apoptosis
Background: PIB PET and CSF Ab42 demonstrate a highly significant inverse correlation. Both are presumed to measure brain Ab amyloid load. Our objective was to develop a method to transform CSF Ab42 measures into calculated PIB measures (PIBcalc) and to partially validate the method in an independent sample of subjects. Methods: Forty-one ADNI subjects underwent PIB PET imaging and lumbar puncture (LP) at the same time. This sample, referred to as the ‘‘training’’ sample, (9 cognitively normal (CN), 22 MCI, and 10 AD), was used to develop a regression model by which CSF Ab42 (with APOE e4 genotype as a covariate) was transformed into units of PIB retention ratio (PIBcalc). A second sample of 362 (105 CN, 164 MCI, 93AD) ADNI subjects underwent LP but not PIB PET imaging and were labeled the ‘‘test’’ data set. Using a multiple imputation measurement error (MIME) model approach, for each subject in the test data set, 100 plausible PIBcalc values were generated from the model. Results: Fig 1 is a log-log plot of PIB PET ratio vs. CSF Ab42 in the training sample (n1⁄4 41). Fig 2 is a plot of PIBcalc values (derived from CSF Ab42) vs. actual PIB PET values in the 41 subject training sample, illustrating good prediction of actual PIB PET from CSF Ab42 obtained at the same time. Fig 3 is a plot of PIBcalc (from CSF Ab42) in the 362 test sample of ADNI subjects who underwent LP but not PIB PET imaging. Conclusions: Brain Ab amyloid load can be measured either by CSF or PET imaging. Some would argue that brain Ab amyloid must be established in all subjects for inclusion in anti amyloid therapeutic trials; however, this may not be possible in all subjects in a study by a single method. Our data supports the conclusion that CSF Ab42 measures of Ab amyloid can be transformed into calculated PIB (PIBcalc) units. Clinical trials can be performed with brain Ab amyloid load measured by either CSF or amyloid PET imaging and the data combined using well established multiple imputation techniques that account for the uncertainty in a CSF-based calculated PIB value.