Comparison of Amyloid PET and CSF Biomarkers for Identifying Early Alzheimer’s Disease

Objective

To compare the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers and amyloid PET for diagnosing early-stage Alzheimer’s disease (AD).

Methods

From the BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). Amyloid-β (Aβ) in 8 brain regions and globally was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 MCI-AD patients from the ADNI study.

Results

The best CSF measures for identifying MCI-AD were Aβ42/T-tau and Aβ42/P-tau (Area Under the Curve, AUC, 0.93–0.94). The best PET measures performed similarly (AUC 0.92; anterior cingulate, posterior cingulate and global neocortical uptake). CSF Aβ42/T-tau and Aβ42/P-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03–0.12, P<0.05). Using non-optimized cutoffs, CSF Aβ42/T-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.

Conclusions

Amyloid PET and CSF biomarkers can identify prodromal AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining CSF and PET. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying prodromal AD can be based on availability, costs and doctor/patient preferences since both have equally high diagnostic accuracy.