Patient Lewy body extracts harm mice and monkeys

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

Ariadna Recasens, Benjamin Dehay, Jordi Bové, Erwan Bezard, Miquel Vila (last author) and colleagues. Annals of Neurology 75(3):351–362, 2014 (DOI 10.1002/ana.24066, PMID 24243558). Funders were not checked.

What happened

Earlier seeding models used synthetic fibrils (landmark 43, landmark 51). The team purified Lewy body fractions from the nigra of postmortem Parkinson's brains and injected them into the substantia nigra or striatum of wild-type mice and macaque monkeys. As controls they used non-Lewy fractions with soluble synuclein from the same tissue.

In both species, the Lewy body extracts caused progressive nigrostriatal degeneration, starting at striatal dopamine terminals. The controls caused none. Human synuclein was taken up by neurons and caused the animals' own synuclein to misfold. Pathological synuclein appeared in the injected neurons and in connected regions, both forward and backward along the pathways. The effects needed both the human synuclein in the extract and the host's own synuclein: the paper states that the effects required host synuclein expression.

Why it moved us toward a cure

It showed that the synuclein in Lewy bodies, as it exists in patients, can start the disease process, and in a species close to humans. That supported antibodies and other drugs that aim at spreading synuclein, and supplied a model that uses patient material.

Outcome

Advanced. The same group later injected patient Lewy body fractions into baboon gut and striatum (Arotcarena et al., Brain 2020;143:1462) and cortex (Teil et al., npj Parkinsons Dis 2023;9:135), but these are follow-ups from the same network, not independent replications. It is a model finding; group sizes were not confirmed in this check.

Sources

• Recasens et al., Ann Neurol 2014, DOI 10.1002/ana.24066, PubMed 24243558
• Arotcarena et al., Brain 2020, DOI 10.1093/brain/awaa096 · Teil et al., npj Parkinsons Dis 2023, DOI 10.1038/s41531-023-00579-w
• Not yet verified: animal numbers and follow-up times; whether an independent lab reproduced the monkey result. The paper drew one commentary (Mov Disord 2014;29:988). No correction or retraction was found (Crossref, Europe PMC); PubPeer could not be reached.