Lumipulse-Measured CSF Biomarkers Can Predict Pathophysiologic Processes in AD

Lumipulse measures of phosphorylated tau (p-tau181) and Aꞵ42 in the cerebrospinal fluid (CSF) accurately identified cognitively normal participants with vs without Alzheimer disease (AD) neuropathologic change, according to study findings published in Neurology.

Researchers conducted a retrospective study of brain donors from the National Alzheimer’s Coordinating Center to determine whether Lumipulse measures of p-tau181, Aꞵ42, and p-tau181/Aꞵ42 in the CSF accurately discriminated cognitively normal patients with AD neuropathologic change from those without AD neuropathologic change. Participants who had Lumipulse-measured CSF Aβ42, t-tau, and p-tau181 biomarker data; normal cognition at lumbar puncture (LP); and available postmortem neuropathology data were eligible for inclusion.

The National Institute on Aging-Alzheimer’s Association criteria were used to stage AD neuropathologic change and categorize participants as either AD- (no or low AD neuropathologic change) or AD+ (intermediate or high AD neuropathologic change).

The 2 primary binary outcome variables were AD+ and AD-. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from binary logistic regressions. In turn, AUC statistics were used to evaluate the accuracy of each biomarker in the discrimination of AD status.

A total of 49 (mean age at death, 87.1; mean age at LP, 79.3; men, 49%; White, 95.9%; mean years of education, 15.9) donated brains were included in the study, of which 20 were AD+. The mean interval between LP and death was 7.76 years.

A baseline model consisting of sex, age at LP, years between LP and death, and APOE ε4 status had an AUC of 0.72 (95% CI, 0.57-0.87; P =.02) for discerning AD+ from AD- brain donors.

After controlling for sex, age at LP, years between LP and death, and APOE ε4 status, a higher CSF p-tau181/Aβ42 ratio strongly and accurately discriminated AD+ and AD- brain donors at autopsy (AUC, 0.97; 95% CI, 0.94-1.00; P =.003). CSF p-tau181 alone was the second-best predictor of AD (AUC, 0.92; 95% CI, 0.84-1.00; P =.001), followed by CSF Aβ42 alone (AUC, 0.92; 95% CI, 0.85-1.00; P =.007). CSF t-tau had the numerically lowest, but still excellent discrimination accuracy for AD status (AUC, 0.87; 95% CI, 0.76-0.97; P =.005).

After removing all covariates, repeat binary logistic regression analysis demonstrated that a higher CSF p-tau181/Aꞵ42 ratio remained a strong and accurate differentiator (AUC, 0.97), followed by CSF Aꞵ42 alone (AUC, 0.91) and CSF p-tau181 alone (AUC, 0.82). The weakest discrimination accuracy for AD status was again exhibited by CSF t-tau (AUC, 0.73).

CSF p-tau181/Aꞵ42 was strongly associated with Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) ratings of neuritic amyloid plaque scores and Braak NFT staging.

The primary limitation of this study was the small and demographically homogeneous sample size.

“Our results encourage the use of LP and CSF biomarker analysis to assist with diagnosis and the identification of optimal candidates for AD-related therapeutics and drug trials,” the study authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.