Alpha-synuclein is what Lewy bodies are made of

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Maria Grazia Spillantini, Marie Luise Schmidt, Virginia Lee, John Trojanowski, Ross Jakes and Michel Goedert (Cambridge and University of Pennsylvania). Funders are not stated in the sources read.

What happened

Lewy bodies, the protein clumps that define Parkinson's under the microscope, had been known since 1912, but their content was unknown. Two months after the SNCA gene report (landmark 4; Science, 27 June 1997), this team's Nature letter (28 August 1997) reported alpha-synuclein in Lewy bodies. A follow-up (Spillantini et al., PNAS 1998) used Lewy bodies from Parkinson's and dementia with Lewy bodies brains: antibodies stained them, the extracted filaments were labelled, and the authors concluded alpha-synuclein is the major filament component. The 1997 letter had no abstract available to me.

Why it moved us toward a cure

It linked the rare genetic form to the common disease through one protein, making alpha-synuclein a target for treatment in most patients.

Outcome

Advanced. It underpins the idea of Parkinson's as a "synucleinopathy" and the 2024 biological definitions of the disease.

Sources

• Spillantini et al., Nature 1997;388:839–840 (DOI; PMID 9278044; citation and dates confirmed in Europe PMC, no abstract)
• Spillantini et al., PNAS 1998;95:6469–6473, DOI 10.1073/pnas.95.11.6469, PMID 9600990
• Not yet verified: the 1997 letter's own wording and whether it examined sporadic cases (the 1998 paper is what supports "mainly made of"); other 1997–98 reports of alpha-synuclein in Lewy bodies.