Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson's disease.
basic_science · Level V
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- Record sourced from PubMed, PMID 42259820.
- Also identified by DOI 10.1038/s41467-026-74083-z.
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Abstract
Lewy bodies, the defining pathological feature of Parkinson's disease, are intraneuronal inclusions enriched in aggregated alpha-synuclein (αSyn). We used correlative light and electron microscopy to selectively investigate phosphorylated αSyn (αSyn<sup>pS129</sup>)-positive inclusions in the substantia nigra of end-stage postmortem Parkinson's disease brain. Here we show that somatic αSyn<sup>pS129</sup> inclusions in nigral dopaminergic neurons are consistently fibrillar, whereas the membranous-type inclusions are restricted to neuritic processes. These neuritic inclusions displayed marked ultrastructural heterogeneity, ranging from predominantly membranous to mixed membranous-fibrillar forms. The selective targeting of defined inclusions enabled detailed structural characterization of Lewy pathology, rather than quantitative or disease-stage comparisons. Our findings highlight clear ultrastructural differences between somatic and neuritic αSyn<sup>pS129</sup> pathology and demonstrate the structural complexity and heterogeneity of Lewy pathology in human Parkinson's disease brain.