Featured ArticleTransforming cerebrospinal fluid Aβ42 measures into calculated Pittsburgh compound B units of brain Aβ amyloid
Introduction
Aβ42 in the cerebrospinal fluid (CSF Aβ42) and positron-emission tomography (PET) imaging of amyloid with Pittsburgh Compound B (PIB) demonstrate a highly significant inverse correlation which has been faithfully replicated in each independent sample in which this correlation has been assessed [1], [2], [3], [4], [5], [6], [7]. Both these techniques are presumed to measure brain Aβ amyloid load [8], [9], [10], [11], [12], [13], [14] (referred to from here on as Aβ load), which is an important disease feature that must be ascertained in individual subjects for many therapeutic and observational studies. However, in some circumstances it may not be possible to measure Aβ load in all subjects in a study by a single method. Our objective was to develop a method to transform CSF Aβ42 measures into calculated PIB measures (PIBcalc) of Aβ load, to partially validate the method in an independent sample of subjects, and illustrate how PIB PET and PIBcalc measures could be pooled in a statistical analysis.
Section snippets
Subjects
Criteria and methods to characterize subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) into diagnostic groups can be found in the report by Petersen et al [15]. A total of 102 ADNI subjects had usable PIB PET imaging data, and a subset of 41 of these subjects underwent both PIB PET and lumbar puncture (LP) at their 12-month visit. This subset, referred to as the “training” sample, consisted of individuals with the following clinical diagnoses: nine subjects were cognitively
Results
Table 1 summarizes the characteristics of the subjects in the training sample. Figure 2A shows the relationship between PIB PET on the y-axis versus CSF Aβ42 on the x-axis in the training sample (n = 41). The data illustrate the expected nonlinear inverse relationship which becomes approximately linear when plotted on the log2 scale (Fig. 2B). The covariates age (P = .32), gender (P = .68), and years of education (P = .66) did not account for a significant amount of variability in PIB PET on
Discussion
Brain Aβ load can be measured either by CSF Aβ42 or PET amyloid imaging. It is increasingly evident that obtaining estimates of brain Aβ load is necessary for many types of research studies in aging and dementia. For example, some would argue that brain Aβ load must be established in all subjects for inclusion in antiamyloid therapeutic trials. In addition, establishing the presence of Aβ amyloid will likely be an important feature of future revised criteria for AD at all clinical stages.
Acknowledgments
The authors acknowledge the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation, U.S.A, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation, U.S.A. The authors thank Denise Reyes and Samantha Wille for Manuscript preparation. This work was supported by the National Institute on Aging (P50 AG16574, U01 AG06786, R01 AG11378, and AG024904) and National Institute of Health Construction Grant (NIH C06
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