Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes

INTRODUCTION: We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET). METHODS: Twenty-three individuals (19 patients, four controls) had CSF measures of amyloid beta (Aβ)(1–42) and total tau/Aβ(1–42) ratio, and florbetapir PET. We compared CSF measures with visual and quantitative (standardized uptake value ratio [SUVR]) PET measures of amyloid. RESULTS: Seventeen of 23 were amyloid-positive on visual reads, and 14 of 23 at an SUVR of ≥1.1. There was concordance (positive/negative on both measures) in 20 of 23, of whom 19 of 20 were correctly classified at an Aβ(1–42) of 630 ng/L, and 20 of 20 on tau/Aβ(1–42) ratio (positive ≥0.88; negative ≤0.34). Three discordant cases had Aβ(1–42) levels between 403 and 729 ng/L and tau/Aβ(1–42) ratios of 0.54–0.58. DISCUSSION: Comparing amyloid PET and CSF biomarkers provides a means of assessing CSF cut points in vivo, and can be applied to small sample sizes. CSF tau/Aβ(1–42) ratio appears robust at predicting amyloid status, although there are gray zones where there remains diagnostic uncertainty.