Objective: To determine whether the alpha-synuclein seed amplification assay (aSyn-SAA) performed on cerebral spinal fluid (CSF) collected at the baseline (BL) PPMI visit is concordant with the detection of Lewy body disease (LBD) pathology at autopsy.

Background: The aSyn-SAA has 89–98% diagnostic concordance in clinically defined PD. However, there is limited data on the concordance between aSyn-SAA early after diagnosis and LBD at autopsy.

Method: Since 2017, the Parkinson’s Progression Markers Initiative (PPMI) study has coordinated brain collections for enrolled participants, with 24 brain autopsy results available as of February 2024. Neuropathologic evaluation followed current consensus guidelines for LBD, glial cytoplasmic inclusions (GCI), Alzheimer’s disease neuropathologic change, hippocampal sclerosis, vascular brain injury, primary age-related tauopathy, limbic-predominant age-related TDP-43 encephalopathy, age-related tau astrogliopathy, and chronic traumatic encephalopathy[1].

Results: aSyn-SAA results were available for 20 participants with brain autopsy [table 1], including 19 enrolled in the PD cohort and one enrolled in the prodromal cohort with REM Sleep Behavior Disorder (RBD). Of the 12 with a BL sporadic PD diagnosis, 11 had aSyn-SAA detected on BL CSF; all of whom had LBD at autopsy. In addition, most had moderate to severe substantia nigra (SN) depigmentation and locus coeruleus (LC) depigmentation. Of the PD GBA carriers, all 4 had aSyn-SAA detected on BL CSF; all of whom had LBD at autopsy, all with moderate to severe SN depigmentation and mild to moderate LC depigmentation. Of the 3 PD LRRK2 carriers, 2 had aSyn-SAA detected on BL CSF, both of whom had LBD at autopsy, both with moderate SN depigmentation and mild to moderate LC depigmentation. One LRRK2 PD was aSyn-SAA not detected on BL CSF and at autopsy showed no LBD but moderate SN depigmentation with no LC depigmentation. One participant enrolled as sporadic PD had aSyn-SAA not detected at BL, who showed GCI at autopsy with no LBD. Finally, the one participant enrolled as RBD had aSyn-SAA detected at BL, 6-, 12-, 24-, 36-, and 48- months and was diagnosed with dementia with Lewy bodies 36 months after BL; autopsy showed LBD with moderate SN and LC depigmentation.

Conclusion: In the PPMI cohort, aSyn-SAA detected/not-detected at enrollment was 100% concordant with the presence/absence of LBD at autopsy.

Table 1

References: [1]Bukhari SA, Nudelman KNH, Rumbaugh M, Richeson P, Fox EJ, Montine KS, Aldecoa I, Garrido A, Franz J, Stadelmann C, Vonsattel JPG, Poston KL, Foroud TM, Montine TJ; Parkinson’s Progression Markers Initiative. Parkinson’s Progression Markers Initiative brain autopsy program. Parkinsonism Relat Disord. 2022 Aug;101:62-65.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/concordance-of-neuropathologic-diagnosis-of-lewy-body-disease-with-baseline-alpha-synuclein-seed-amplification-assay-in-ppmi/