Seed amplification assay

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

Andrew Siderowf, Luis Concha-Marambio, Claudio Soto, Kenneth Marek and colleagues in the Parkinson's Progression Markers Initiative (PPMI). PPMI is run by the Michael J. Fox Foundation; the paper lists the Foundation and the US National Institute on Aging as funders.

What happened

The test amplifies tiny amounts of misfolded alpha-synuclein in spinal fluid until it can be detected. In 1,123 PPMI participants (545 with Parkinson's, 163 healthy controls) sensitivity for Parkinson's was 87.7% and specificity in controls 96.3%. The test missed more people in some groups: 67.5% of LRRK2 Parkinson's and 78.3% of sporadic cases without loss of smell were positive. It was positive in 44 of 51 (86%) people with REM sleep behaviour disorder or reduced smell, and in 25 of 310 (8%) symptom-free carriers of LRRK2 or GBA variants.

Why it moved us toward a cure

For the first time, trials of slowing drugs can confirm that participants have the target biology. In 2024 it led to two competing biological definitions of the disease (NSD-ISS and SynNeurGe).

Earlier CSF tests measured total synuclein, which overlapped too much between groups to use (landmark 275).

Outcome

Advanced, now used to select trial participants. It shows whether pathology is present, not how fast it is progressing.

The Foundation then funded work to make the test quantitative, measuring how much abnormal synuclein is present rather than only whether it is there. On 30 May 2024 it announced $9.75 million for five teams, three of them on quantitative seed assays (a blood test; a skin-based test from Concha-Marambio and Foroud; Knowles's microfluidics) and two on synuclein PET tracers (landmark 116) (MJFF release). In June and July 2025 it funded five more quantification projects worth over $4 million (MJFF, 20 Aug 2025). The FDA backed the assay for trial enrichment in August 2024 (landmark 346). The Foundation's own year-end reviews give running totals: more than $18 million awarded to quantitative biomarker teams by the end of 2024 (2024 Year in Review), and more than 20 grants through its QBio programme, with nearly $100 million committed by two leadership funders, by 2025 (2025 Year in Review). These totals are the Foundation's figures, not independently checked.

Sources

• MJFF, 30 May 2024: $9.75 million for quantitative biomarkers; MJFF, 20 Aug 2025: five quantification grants (funding facts only)
• Siderowf et al., Lancet Neurol 2023;22:407–417 (DOI 10.1016/S1474-4422(23)00109-6, PMID 37059509). No correction or retraction is listed; PubMed lists six commentaries.
• Alzforum on the 2024 frameworks
• NSD-ISS paper (MJFF PDF)