O1‐02‐08: Transforming CSF Aβ42 measures of brain beta‐amyloid into calculated PIB (PIBcalc) units
Clifford R. Jack, Stephen D. Weigand, Prashanthi Vemuri, Heather J. Wiste, Paul S. S. Aisen, Ronald Carl Petersen, Michael Walter Weiner, David S. Knopman, Leslie M. Shaw, John Q. Trojanowski · Alzheimer s & Dementia · 2010
PIB PET and CSF Aβ42 demonstrate a highly significant inverse correlation. Both are presumed to measure brain Aβ amyloid load. Our objective was to develop a method to transform CSF Aβ42 measures into calculated PIB measures (PIBcalc) and to partially validate the method in an independent sample of subjects. 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 Aβ42 (with APOE ∊4 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. Fig 1 is a log-log plot of PIB PET ratio vs. CSF Aβ42 in the training sample (n = 41). Fig 2 is a plot of PIBcalc values (derived from CSF Aβ42) vs. actual PIB PET values in the 41 subject training sample, illustrating good prediction of actual PIB PET from CSF Aβ42 obtained at the same time. Fig 3 is a plot of PIBcalc (from CSF Aβ42) in the 362 test sample of ADNI subjects who underwent LP but not PIB PET imaging. Brain Aβ amyloid load can be measured either by CSF or PET imaging. Some would argue that brain Aβ 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 Aβ42 measures of Aβ amyloid can be transformed into calculated PIB (PIBcalc) units. Clinical trials can be performed with brain Aβ 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.