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Fluorescence Detection of Alpha-Synuclein Aggregates in the Gut Using a Peptide Probe
Rachel Sim1, Jeremy Lee1, Joey Chieng1
1Institute of Molecular and Cell Biology, Agency for Science, Research and Technology (A*STAR), 31 Biopolis Way, Singapore 138669, Republic of Singapore.
ACS Chemical Neuroscience
|March 2, 2026
Summary
A new peptide probe, P1, can detect alpha-synuclein aggregates in the gastrointestinal tract, offering a potential early diagnostic marker for Parkinson's disease (PD). This fluorescence imaging tool shows promise for identifying PD risk through colonic biopsies.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Gastroenterology
Background:
- Parkinson's disease (PD) diagnosis relies on motor symptoms, by which time irreversible neurodegeneration has occurred.
- Pathological alpha-synuclein (α-syn) aggregates in the gastrointestinal tract present a potential target for early PD diagnosis.
Purpose of the Study:
- To develop and evaluate a peptide-based fluorescent probe (P1) for specific labeling of α-syn aggregates in the gastrointestinal tract.
- To assess the potential of P1 as an early diagnostic biomarker for Parkinson's disease risk.
Main Methods:
- Utilized primary hippocampal neuronal cells and wild-type mouse tissues incubated with preformed α-syn fibrils (PFFs).
- Tested peptide probe P1 for its accuracy and specificity in labeling α-syn aggregates compared to an antibody.
- Evaluated P1's performance in various gastrointestinal tissues from PFF-injected and transgenic mice.
Main Results:
- Probe P1 demonstrated high accuracy (87%) and specificity for staining aggregated α-syn over monomeric forms.
- P1 successfully labeled α-syn aggregates across gastrointestinal tissue layers, comparable to antibody staining.
- Increased probe labeling correlated with age, indicating higher α-syn aggregate accumulation in older mice.
Conclusions:
- Probe P1 is a promising tool for detecting α-syn aggregates in the colon, even with brief sample flushing.
- P1 shows potential for use in colonic biopsies and intact colon imaging for early PD risk assessment.
- Further development of P1 as a fluorescent imaging biomarker for colonic α-syn aggregates is supported.
