Stage-Dependent Agreement between Cerebrospinal Fluid Proteins and FDG-PET Findings in Alzheimer's Disease

Cerebral hypometabolism and abnormal levels of amyloid beta (A beta), total (t-tau) and phosphorylated tau (p-tau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 +/- 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [F-18]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of A beta(1-42), p-tau(181), and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE >20 points, n=30) and moderate (MMSE <21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [kappa]=0.34, p=0.016) for t-tau, 68% (kappa=0.10, n.s.) for p-tau(181), and 68% (kappa=0.04, n.s.) for A beta(1-42). No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, kappa=0.77, p=0.001) and p-tau(181) (88%, kappa=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage.