Study Rationale: Mixed pathology is common in all neurodegenerative diseases including Parkinson’s disease (PD). Three cerebrospinal fluid (CSF) biomarkers, Ab1-42, t-tau and p-tau181, provide an index to the hallmark pathologic markers of Alzheimer’s disease (AD) pathology, namely, plaques and tangles. Thus we measured these three biomarkers in CSF of BioFIND PD and healthy matched controls in order to detect the presence, or absence, of AD pathology in these study participants.
Hypothesis: In this study we are testing the hypothesis that AD pathology, detected by measurement of the CSF AD biomarkers, Ab1-42, t-tau and p-tau181, is present in some moderate to advanced stage PD patients and is associated with a greater rate of cognitive decline as measured by the Montreal Cognitive Assessment test.
Study Design: The study participants included 108 patients with moderate to advanced stage PD and 85 healthy matched controls, each of whom underwent lumbar puncture to provide CSF at study entry. The three AD biomarkers, Ab1-42, t-tau and p-tau181, were measured, using a validated immunoassay method, in aliquots of each of the CSF samples. Following completion of these analytical runs to determine the concentrations of the AD biomarkers, including analyses of quality control CSF samples, statistical analyses were performed to test for predictive performance of the CSF AD biomarkers for cognitive decline subsequent to the date of the lumbar puncture.
Impact on Diagnosis/Treatment of Parkinson’s disease: These data taken together with the CSF a-SYN data that reflects the presence of the hallmark pathologic finding in PD patients of Lewy bodies, provide an important characterization of PD and AD neuropathology in BioFIND patients. These results provide the framework for exploring CSF biomarker changes and predictive performance for detection of cognitive decline across the disease continuum from early stage PD (PPMI study) to moderate to advanced stage PD (BioFIND study). These findings provide the basis for future prospective studies in PD patients to establish how early in the disease process these AD and PD neuropathologic processes are detectable to enable future drug trials to intervene at the earliest possible stages of these in PD patients.
Next Steps for Development: These findings can provide the basis for expanded studies in early stage PD to expand the numbers of study subjects and enable robust exploration of the utility of algorithms that combine CSF a-SYN and the AD biomarkers Ab1-42, t-tau and p-tau181 for prediction of cognitive decline.