The cerebrospinal fluid Aβ1-42/Aβ1-40 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-beta (A beta) increases when the CSF A beta(1-42)/A beta(1-40) ratio is used as compared to CSF A beta(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 [F-18] Florbetapir ([F-18]AV45) PET scan, [F-18] 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 (A beta(1-42), A beta(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 (VT)) [F-18]AV45 PET measures when the CSF A beta(1-42)/A beta(1-40) was applied compared to A beta(1-42) alone. CSF biomarkers were stronger associated to [F-18]AV45 PET for SUVR values when considering the total brain white matter as reference region instead of cerebellar grey matter Conclusion: The concordance between CSF A beta and [F-18]AV45 PET increases when the CSF A beta(1-42)/A beta(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.

Jaar van publicatie:2017

Trefwoorden:A1 Journal article

BOF-keylabel:ja

BOF-publication weight:1

CSS-citation score:2

Authors from:Higher Education

Toegankelijkheid:Open