Use of amyloid-PET to determine cutpoints for CSF markers A multicenter study

Objectives:To define CSF -amyloid 1-42 (A(42)) cutpoints to detect cortical amyloid deposition as assessed by C-11-Pittsburgh compound B ([C-11]PiB)-PET and to compare these calculated cutpoints with cutpoints currently used in clinical practice.Methods:We included 433 participants (57 controls, 99 with mild cognitive impairment, 195 with Alzheimer disease [AD] dementia, and 82 with non-AD dementia) from 5 European centers. We calculated for each center and for the pooled cohort CSF A(42) and A(42)/tau ratio cutpoints for cortical amyloid deposition based on visual interpretation of [C-11]PiB-PET images.Results:Amyloid-PET-based calculated CSF A(42) cutpoints ranged from 521 to 616 pg/mL, whereas existing clinical-based cutpoints ranged from 400 to 550 pg/mL. Using the calculated cutpoint from the pooled sample (557 pg/mL), concordance between CSF A(42) and amyloid-PET was 84%. Similar concordance was found when using a dichotomized A(42)/tau ratio. Exploratory analysis showed that participants with a positive amyloid-PET and normal CSF A(42) levels had higher CSF tau and phosphorylated tau levels and more often had mild cognitive impairment or AD dementia compared with participants who had negative amyloid-PET and abnormal CSF A(42) levels.Conclusions:Amyloid-PET-based CSF A(42) cutpoints were higher and tended to reduce intercenter variability compared with clinical-based cutpoints. Discordant participants with normal CSF A(42) and a positive amyloid-PET may be more likely to have AD-related amyloid pathology than participants with abnormal CSF A(42) and a negative amyloid-PET.Classification of evidence:This study provides Class II evidence that an amyloid-PET-based CSF A(42) cutpoint identifies individuals with amyloid deposition with a sensitivity of 87% and specificity of 80%.