Objective: To examine the relationship between biofluid biomarkers and post-mortem pathological findings in autopsied subjects from the Parkinson’s Progression Marker Initiative (PPMI).

Background: The PPMI study has collected longitudinal biofluid biomarker data in patients with Parkinson’s disease. Some patients have come to autopsy, offering a unique opportunity to examine the relationship between these biomarkers and neuropathology.

Method: CSF Aβ1-42, total-tau (t-tau), and phosphorylated tau (p-tau181) were measured using Elecsys automated electrochemiluminescence assays (Roche). Total CSF alpha-synuclein (αSyn) was measured using a commercially available ELISA assay (Biolegend). Serum neurofilament light chain (NfL) was measured using a Simoa NfL assay (Quanterix). Autopsies were performed per local institutional methods but included immunohistochemical evaluations of alpha-synuclein, tau, and amyloid-beta and TDP-43 pathology allowing for staging of Lewy body disease and common co-pathologies (1). Data were downloaded on 2/21/2023 from the PPMI database (www.ppmi-info.org).

Results: Data from 17 autopsied subjects were available. One subject had multiple systems atrophy; another had a LRRK2 G2019S mutation and no Lewy body pathology. The 15 remaining cases were Braak Lewy body stage 5 or 6/6. Nine cases had no or low levels of AD neuropathological change (PD-ADNC), 6 had intermediate or high levels of ADNC (PD+ADNC). Age of onset and disease duration was similar between PD-ADNC and PD+ADNC (p=0.9). MoCA scores declined faster in PD+ADNC over time (p<.001). CSF Ptau181/Aβ1-42 and T-tau/Aβ1-42 ratios were elevated in PD+ADNC compared to PD-ADNC at the last available testing prior to autopsy when controlling for this interval (p=.04 and .02; interval: 5.4 ±1.6 years). CSF total αSyn was similar between groups (p=.5). Longitudinal models showed that Ptau181/Aβ1-42, T-tau/Aβ1-42 ratios and serum NfL increased more for PD+ADNC over time (p=.001, .040 and .001).

Conclusion: Alzheimer’s disease co-pathology is common and associated with more rapid cognitive decline in the PPMI cohort. CSF evaluations can identify the presence of such co-pathology in vivo. The addition of more participants will allow for greater characterization of the relationship between longitudinal changes of biofluid biomarkers, clinical features, and histopathological features.

References: 1. Bukhari SA, Nudelman KN, Rumbaugh M, Richeson P, Fox EJ, Montine KS, Aldecoa I, Garrido A, Franz J, Stadelmann C, Vonsattel JP. Parkinson’s Progression Markers Initiative brain autopsy program. Parkinsonism & Related Disorders. 2022 Aug 1;101:62-5.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alzheimers-disease-co-pathology-and-its-influence-on-biofluid-biomarkers-in-autopsied-subjects-from-the-ppmi-study/