Transforming cerebrospinal fluid Aß42 measures into calculated Pittsburgh Compound B units of brain Aß amyloid.

ABSTRACT

BACKGROUND: Positron-emission tomography (PET) imaging of amyloid with Pittsburgh Compound B (PIB) and Aß42 levels in the cerebrospinal fluid (CSF Aß42) demonstrate a highly significant inverse correlation. Both these techniques are presumed to measure brain Aß amyloid load. The objectives of this study were to develop a method to transform CSF Aß42 measures into calculated PIB measures (PIBcalc) of Aß amyloid load, and to partially validate the method in an independent sample of subjects. METHODS: In all, 41 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent PIB PET imaging and lumbar puncture (LP) at the same time. This sample, referred to as the "training" sample (nine cognitively normal subjects, 22 subjects with mild cognitive impairment, and 10 subjects with Alzheimer's disease), was used to develop a regression model by which CSF Aß42 (with apolipoprotein E ɛ4 carrier status as a covariate) was transformed into units of PIB PET (PIBcalc). An independent "supporting" sample of 362 ADNI subjects (105 cognitively normal subjects, 164 subjects with mild cognitive impairment, and 93 subjects with Alzheimer's disease) who underwent LP but not PIB PET imaging had their CSF Aß42 values converted to PIBcalc. These values were compared with the overall PIB PET distribution found in the ADNI subjects (n=102). RESULTS: A linear regression model demonstrates good prediction of actual PIB PET from CSF Aß42 measures obtained in the training sample (R(2)=0.77, P<.001). PIBcalc data (derived from CSF Aß42) in the supporting sample of 362 ADNI subjects who underwent LP but not PIB PET imaging demonstrate group-wise distributions that are highly consistent with the larger ADNI PIB PET distribution and with published PIB PET imaging studies. CONCLUSION: Although the precise parameters of this model are specific for the ADNI sample, we conclude that CSF Aß42 can be transformed into PIBcalc measures of Aß amyloid load. Brain Aß amyloid load can be ascertained at baseline in therapeutic or observational studies by either CSF or amyloid PET imaging and the data can be pooled using well-established multiple imputation techniques that account for the uncertainty in a CSF-based PIBcalc value.