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Updated: Jun 22, 2025
Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid
Published on: December 4, 2017
CSF Proteomics in Patients With Progressive Supranuclear Palsy.
Amy Wise1, Jingyao Li1, Mai Yamakawa1
1From the Weill Institute for Neurosciences (A.W., L.M., H.W.H., A.L.-L., A.M.S., A.C., J.T., P.A.L., L.V., L.T.G., S.S., W.W.S., B.L.M., J.C.R., A.L.B.), Department of Neurology, Memory and Aging Center, University of California, San Francisco; Novartis Institutes for Biomedical Research, Inc. (J. Li, J. Loureiro, B.P., K.W., R.S., J.-A.P.), Cambridge, MA; Department of Neurology (M.Y., J.R.), University of California, Los Angeles; The Bluefield Project to Cure FTD (L.M.); Department of Neurology (B.F.B.), Mayo Clinic, Rochester, MN; Department of Neurology (B.C.D., A.-M.A.W.), Massachusetts General Hospital and Harvard Medical School, Boston; Department of Neurology (M.G.), University of Pennsylvania, Philadelphia; Department of Neurology (I.L.), University of California, San Diego; Department of Neurology (A.P.), Johns Hopkins University, Baltimore, MD; Department of Neurology (M.C.T.), University of Toronto, Ontario, Canada; and Departments of Mathematics and Statistics (Z.Z.), University of California, Los Angeles.
This study identified novel cerebrospinal fluid (CSF) biomarkers for progressive supranuclear palsy (PSP) using aptamer proteomics. Axon guidance pathway proteins were notably downregulated in PSP, offering potential targets for future diagnostics and therapeutics.
Area of Science:
- Neuroscience
- Proteomics
- Biomarker Discovery
Background:
- Progressive supranuclear palsy (PSP) lacks definitive fluid biomarkers, hindering therapeutic development.
- Unbiased aptamer-based proteomics was employed to discover novel biomarkers in CSF for PSP.
Purpose of the Study:
- To identify and validate novel cerebrospinal fluid (CSF) protein biomarkers for progressive supranuclear palsy (PSP).
- To explore the diagnostic utility and association with disease severity of identified biomarkers.
Main Methods:
- Cross-sectional study utilizing DNA aptamer (SOMAmer) proteomics on CSF samples from clinically diagnosed PSP and healthy controls.
- Analysis across three cohorts: original, validation, and neuropathology-confirmed, using SomaScan platforms.
- Statistical analyses included differential expression, pathway enrichment, coexpression network analysis, ROC curves, and linear regression for clinical severity correlation.
Main Results:
- Multiple SOMAmers showed differential expression in PSP cohorts, with most exhibiting reduced signal.
- Synaptic function/JAK-STAT, vesicle cytoskeletal trafficking, and cytokine-cytokine receptor interaction pathways were associated with PSP.
- Axon guidance pathway proteins were significantly downregulated in PSP across all cohorts and demonstrated high diagnostic accuracy (AUC > 0.815).
- Two inflammatory proteins, galectin-10 and CTLA-4, correlated with PSP clinical severity scores.
Conclusions:
- Downregulation of axon guidance pathway proteins and other molecular pathways is characteristic of PSP.
- These proteins represent promising candidates for PSP biomarker and therapeutic development.
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