Parkinson’s Progression Markers Initiative (PPMI) Biofluid Biomarkers Program

This Parkinson’s Progression Markers Initiative (PPMI) program seeks to identify collaborators who have analytically validated biomarker assays to deploy in existing PPMI biosamples to enhance the biological definition of Parkinson’s disease (PD) and related disorders, both before and after symptom onset.

Projects must address the following strategic goals:

• Identify biomarkers of alpha-synuclein pathology beyond the alpha-synuclein seed amplification assay.
• Understand biologic endotypes of initiation/progression of PD using targeted/unbiased omics.
• Comprehensively characterize known biomarkers of dementia, neurodegeneration and copathology.
• Advance characterization across the progression of PD to predict and correlate with progression on motor, cognitive and other clinical domains.

This project aims to enhance the biological definition of Parkinson’s disease and related disorders, both before and after symptom onset. Selected projects must evaluate biomarkers that could improve the classification and staging of PD by:

• Identifying early biological changes and how they relate to f key biomarkers, including the alpha-synuclein seed amplification assay (SAA), dopamine loss and symptom onset.
• Predicting how PD progresses based on biomarker and clinical outcomes, such as movement and cognition.
• Correlating progression of biomarkers and clinical outcomes of PD.
• Defining biologically distinct subgroups of people with PD.
• Investigating disease mechanisms in cases without alpha-synuclein aggregates (e.g., alpha-synuclein SAA-negative LRRK2 PD) and in related conditions like multiple system atrophy (MSA).

To be considered for funding, the biomarker assay must fulfill one or more of the criteria above, be analytically validated and deployable in existing PPMI biosamples (see inventory here: https://www.ppmi-info.org/access-data-specimens/specimens).

The program will support the following work in PPMI biosamples:

• Quantitative, known biomarkers of neurodegeneration (ex. amyloid, tau, TDP-43, NfL) in existing biofluids.
• Biomarker discovery using targeted, multiplexed panels excluding proteomics.
• Pathway focused biomarkers such as mitochondrial dysfunction, immune dysfunction/inflammation and endolysosomal dysfunction to support biological subtyping.
• Alpha-synuclein pathology biomarkers with priority to those that are quantitative.

When considering proposals submitted to this program, MJFF will prioritize those that:

• Situate the proposed molecular bioassay analysis within the breadth of existing PPMI clinical, imaging, genetic and other molecular data.
• Establish a clear link to at least one of the strategic goals listed above.
• Evaluate the proposed biomarker for a specific context of use.

Important to Note: Projects funded through this program will be established as collaborations between the awardee and PPMI. Study leadership intends to work closely with funded investigators by providing active thought leadership throughout the project, guidance on sample selection and statistical support. All biosample/funding recipients must abide by PPMI’s open data principles by depositing data into its publicly accessible database prior to becoming unblinded to subject IDs and PD status and adhering to MJFF’s publication policy.