Diagnostic value of cerebrospinal fluid Aβ ratios in preclinical Alzheimer’s disease

Introduction: In this study of preclinical Alzheimer’s disease (AD) we assessed the addeddiagnostic value of using cerebrospinal fluid (CSF) Aβ ratios rather than Aβ42 in isolation fordetecting individuals who are positive on amyloid positron emission tomography (PET).Methods: Thirty-eight community-recruited cognitively intact older adults (mean age 73, range65-80 years) underwent 18F-flutemetamol PET and CSF measurement of Aβ1-42, Aβ1-40,Aβ1-38, and total tau (ttau). 18F-flutemetamol retention was quantified using standardizeduptake value ratios in a composite cortical region (SUVRcomp) with reference to cerebellar greymatter. Based on a prior autopsy validation study, the SUVRcomp cut-off was 1.57. Sensitivities,specificities and cut-offs were defined based on receiver operating characteristic analysis withCSF analytes as variables of interest and 18F-flutemetamol positivity as the classifier. We alsodetermined sensitivities and CSF cut-off values at fixed specificities of 90% and 95%.Results: Seven out of 38 subjects (18%) were positive on amyloid PET. Aβ42/ttau, Aβ42/Aβ40,Aβ42/Aβ38, and Aβ42 had the highest accuracy to identify amyloid-positive subjects (areaunder the curve (AUC) ≥ 0.908). Aβ40 and Aβ38 had significantly lower discriminative power(AUC = 0.571). When specificity was fixed at 90% and 95%, Aβ42/ttau had the highestsensitivity among the different CSF markers (85.71% and 71.43%, respectively). Sensitivity ofAβ42 alone was significantly lower under these conditions (57.14% and 42.86%, respectively).Conclusion: For the CSF-based definition of preclinical AD, if a high specificity is required,our data support the use of Aβ42/ttau rather than using Aβ42 in isolation.

Publication year:2015