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

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).

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.

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.

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.