Lewy pathologies in sporadic versus <em>SNCA </em>mutation Parkinson’s disease — The Association Specialists

Lewy pathologies in sporadic versus SNCA mutation Parkinson’s disease (21558)

Giselle Sagredo 1 2 , Hongyun Li 1 2 , Ping Wu 1 2 , YuHong Fu 1 2 , Glenda Halliday 1 2
  1. Brain and Mind Centre and Faculty of Medicine and Health School of Medical Sciences, The University of Sydney, Sydney, NSW, Australia
  2. Aligning Science Across Parkinson's (ASAP) Collaborative Research Network , Chevy Chase, MD, 20815

Aim: To compare the types of Lewy pathology (LP) in post-mortem cortical tissue between SNCA mutation and sporadic Parkinson’s disease (PD).

Methods: Formalin-fixed paraffin-embedded post-mortem cingulate cortex from fifteen sporadic, two A53T, one G51D, and two E46K SNCA mutation cases were assessed (approved 2020/707) with multiplexed immunofluorescence labelling using scanner and confocal imaging. The colocalisation of proteins was determined and the proportion of the neurons with LP identified. Control cases had no discernable cortical LPs.

Results: LP were identified in neurons as puncta, or solid or mixed Lewy body (LB) deposits with all LBs colocalising p62. In all sporadic and SNCA-related cases, LBs were found in ~10% of neurons which concentrated in lower cortical layers. An additional 10% of cortical neurons in SNCA-related but not sporadic PD cases had a-syn puncta (50% colocalized p62 and a high proportion colocalised with RhoA, a small GTPase). Sporadic PD had mainly solid round LBs whereas nearly 50% of LBs in SNCA-related PD had mixed morphology. All LBs colocalised phosphorylated tau protein and over 50% of LBs in sporadic and E46K-mutant PD colocalised RhoA.

Conclusion: There are significant differences in the types of cortical LP in sporadic versus SNCA-related PD, with sporadic cases having a largely uniform population of matured solid LBs while SNCA mutation cases had a substantial amount of progressing LB types. Cortical LBs in A53T and G51D cases had limited RhoA colocalisation. These data suggest that the type and progression of cortical LB formation may differ between sporadic and SNCA cases.