The Cerebrospinal Fluid Aβ(1–42)/Aβ(1–40) Ratio Improves Concordance with Amyloid-PET for Diagnosing Alzheimer’s Disease in a Clinical Setting

BACKGROUND: Evidence suggests that the concordance between amyloid-PET and cerebrospinal fluid (CSF) amyloid-β (Aβ) increases when the CSF Aβ(1–42)/Aβ(1–40) ratio is used as compared to CSF Aβ(1–42) levels alone. OBJECTIVE: In order to test this hypothesis, we set up a prospective longitudinal study comparing the concordance between different amyloid biomarkers for Alzheimer’s disease (AD) in a clinical setting. METHODS: Seventy-eight subjects (AD dementia (n = 17), mild cognitive impairment (MCI, n = 48), and cognitively healthy controls (n = 13)) underwent a [(18)F]Florbetapir ([(18)F]AV45) PET scan, [(18)F]FDG PET scan, MRI scan, and an extensive neuropsychological examination. In a large subset (n = 67), a lumbar puncture was performed and AD biomarkers were analyzed (Aβ(1–42), Aβ(1–40), T-tau, P-tau(181)). RESULTS: We detected an increased concordance in the visual and quantitative (standardized uptake value ratio (SUVR) and total volume of distribution (V(T))) [(18)F]AV45 PET measures when the CSF Aβ(1–42)/Aβ(1–40) was applied compared to Aβ(1–42) alone. CSF biomarkers were stronger associated to [(18)F]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matter CONCLUSIONS: The concordance between CSF Aβ and [(18)F]AV45 PET increases when the CSF Aβ(1–42)/Aβ(1–40) ratio is applied. This finding is of most importance for the biomarker-based diagnosis of AD as well as for selection of subjects for clinical trials with potential disease-modifying therapies for AD.