Correlation of CSF Biomarkers with Cognitive Screening Tests and PET Scan: A Tandem Approach

Testing for amyloid beta protein (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau at position 181: p-Tau 181) in CSF using Roche Elecsys assays has been approved by the FDA as biomarkers for Alzheimer's disease. We studied correlation between pTau181/Aβ42 ratios (>0.023 positive cutoff), screening for cognitive functions (commonly used for screening patients suspected of dementia and AD) with actual AD diagnosis based on PET scans in 143 patients.

All Roche Elecsys (electrochemiluminescence) assays for biomarkers were run on Cobas e 801 analyzer. Imaging studies were performed using fluorodeoxyglucose PET scans. Screening patients for cognitive functions (SCFs) included either MOCA, SLUMS, STMS, or MMSE.

Out of 143 patients with CSF AD biomarker ratios studied, 80 patients showed positive values (mean: 0.0555), while 63 patients showed negative ratios (mean: 0.0138). We also compared biomarker results with PET imaging in 40 patients (PET scan results were not available for all patients). Chi-square analysis showed a statistically significant association between positive CSF biomarker tests and PET scans {X²(1, N=40)=14.593; p<0.01}. In contrast, we observed poor correlation between SCFs and PET scan results using chi-square analysis {X²(1, N=40)=3.558, p=0.059}. However, binary logistic regression demonstrated a combination of abnormal SCF and a positive CSF screen significantly predicted a positive imaging result {X²(2, N=40)=15.940, p<.001}.

CSF pTau181/Aβ42 ratios correlated significantly better with PET scan findings compared to various SCFs. Furthermore, a combination approach that included SCF and CSF biomarkers provided better correlation with positive PET imaging.