Proteomic profiling in cerebrospinal fluid: advancing biomarker discovery in neurology

With nearly 100 million people in the United States alone suffering from a neurologic disease, there is an urgent need for reliable biomarkers to aid in diagnosis, monitoring, and development of new treatments.1,2 Historically, neurology has relied on cognitive tests, imaging, and analysis of postmortem brain tissue to understand neurologic diseases.3 Proteomic technologies that can analyze complex body fluids such as cerebrospinal fluid (CSF) and blood can provide a more dynamic picture of molecular events occurring at preclinical stages of disease, offering opportunities for earlier detection and intervention.2,4

The case for cerebrospinal fluid in protein profiling

A complex fluid matrix composed of proteins and lipids, CSF is the only body fluid in direct contact with the central nervous system and offers a window into the living brain.2,3,5 CSF provides a unique opportunity to identify potential biomarkers for understanding neurologic disease pathology and progression. Since only 20% of total CSF protein is derived from the brain, the ability to measure a large number of proteins across a wide dynamic range is critical.6

The SomaScan® Assay for biomarker discovery in neurologic diseases

The SomaScan Assay can detect 7,000 proteins simultaneously, with a 10-log dynamic range, from fmol – µmol sensitivity.7 The SomaScan Assay has been successfully used in proteomic studies of CSF (and other sample types) for a variety of neurogenerative diseases. The following publications demonstrate unique research studies related to Alzheimer’s disease (AD), neuropsychiatric systemic lupus erythematosus (NPSLE), and multiple sclerosis (MS).8-10

New treatment targets for Alzheimer’s disease8
Based on data from Yang et al. Nat Neurosci. 2021;24(9):1302-1312. doi:10.1038/s41593-021-00886-6
Challenge Genetic studies alone have fallen short in identifying causal factors of
neurologic diseases and new treatment targets.
Solution Researchers used the SomaScan Assay to profile 1,305 proteins in the brain,
CSF, and plasma from participants with or without AD. Combining proteomic
and genetic data, they identified potential drug targets for neurologic diseases.
Key findings
  • CSF and plasma each shared more than 70% of brain protein quantitative
    trait loci (pQTLs), suggesting that both sample types directly reflect
    neurologic processes.
  • pQTLs were then linked to different neurologic disease outcomes. In CSF, the
    results showed:

    • 3 proteins that correlated with the risk of AD
    • 18 proteins that correlated with the progression of AD
    • 8 proteins that correlated with the age at onset of AD
    • 13 proteins that correlated with the risk of Parkinson’s disease
    • 1 protein that correlated with the risk of frontotemporal dementia
    • 7 proteins that correlated with the risk of stroke
  • This study points to repurposing opportunities for 25 drugs known to interact
    with the identified proteins.


Biomarkers for neuropsychiatric systemic lupus erythematosus9Based on data from Vanarsa et al. Arthritis Rheumatol. 2022;74(7):1223-1234. doi:10.1002/art.42080
Challenge Currently, there is no gold standard diagnostic test for NPSLE.
Solution Researchers used the SomaScan Assay to compare 1,129 proteins in CSF from
patients with NPSLE or other neurologic diseases.
Key findings 40 CSF proteins were elevated in patients with NPSLE, and thus identified as
potential disease biomarkers.

  • In total, 5 CSF proteins showed potential for use as a NPSLE diagnostic.


Processes that underlie disability progression in multiple sclerosis10Based on data from Masvekar et al. Mult Scler Relat Disord. 2019;28:34-43. doi:10.1016/j.msard.2018.11.032
Challenge The pathogenesis of MS is poorly understood; once the disease reaches the
progressive stage, current treatments are ineffective.
Solution Researchers used the SomaScan Assay to measure more than 1,000 proteins in
the CSF of patients with neuroimmunologic diseases and that of healthy
Key findings The results showed that microglial activation and toxic astrogliosis are
associated with MS and may contribute to destruction of central nervous
system tissue.

  • In patients with MS, a cluster of astrocyte-derived proteins and a cluster of
    microglial-derived proteins were elevated and correlated with MS severity,
    suggesting a pathogenic role.

These 3 neurologic research studies (a previous version of the current SomaScan 4.1 Assay was used in these
studies) demonstrate the extensive discoveries that can be made using the SomaScan Assay for the profiling of
proteins in CSF for neurology research.8-10


  1. Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: a summary report and call to action. Ann Neurol. 2017;81(4):479-484. doi:10.1002/ana.24897.
  2. Hok-A-Hin YS, Willemse EAJ, Teunissen CE, Del Campo M. Guidelines for CSF processing and biobanking: impact on the identification and development of optimal CSF protein biomarkers. In: Santamaría E, Fernández-Irigoyen J, eds. Cerebrospinal Fluid (CSF) Proteomics: Methods in Molecular Biology; vol 2044. Humana; 2019;chap 2. Accessed June 29, 2022. doi:10.1007/978-1-4939-9706-0_2.
  3. Ward M, Schofield EL. Biomarkers for brain disorders. Therapy. 2010;7(4):321-336.
  4. Shi L, Winchester LM, Westwood S, et al. Replication study of plasma proteins relating to Alzheimer’s pathology. Alzheimers Dement. 2021;17(9):1452-1464. doi:10.1002/alz.12322.
  5. Koch S, Donarski N, Goetze K, et al. Characterization of four lipoprotein classes in human cerebrospinal fluid. J Lipid Res. 2001;42(7):1143-1151. doi:10.1016/S0022-2275(20)31605-9.
  6. Reiber H. Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci. 2003;21(3-4):79-96.
  7.  Data on file. SomaLogic Operating Co., Inc.
  8. Yang C, Farias FHG, Ibanez L, et al. Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders. Nat Neurosci. 2021;24(9):1302-1312. doi:10.1038/s41593-021-00886-6.
  9. Vanarsa K, Sasidharan P, Duran V, et al. Aptamer-based screen of neuropsychiatric lupus cerebrospinal fluid reveals potential biomarkers that overlap with the choroid plexus transcriptome. Arthritis Rheumatol. 2022;74(7):1223-1234. doi:10.1002/art.42080.
  10.  Masvekar R, Wu T, Kosa P, Barbour C, Fossati V, Bielekova B. Cerebrospinal fluid biomarkers link toxic astrogliosis and microglial activation to multiple sclerosis severity. Mult Scler Relat Disord. 2019;28:34-43. doi:10.1016/j.msard.2018.11.032.

Share with colleagues

More blogs

BlogUnlocking cancer insights: SomaLogic-EPIC study partnership reveals how lifestyle choices impact risk 

Having provided more insights into the relationship between environmental factors and the incidence of cancer than any other cohort in existence, EPIC has been crucial to understanding how lifestyle influences risk of disease. This is important because current cancer research shows that factors such as tobacco, diet, infection, alcohol, drugs, and chemicals are more important than genetic (hereditary) factors in determining the development of most cancers. In fact, only 5-10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90-95% have their roots in environment and lifestyle.

Learn more

BlogBiomarkers are key to understanding dementia risk, disease pathology, and mechanism of action for new therapeutics

Our team was honored to see so many researchers in academic research groups and pharma companies worldwide present findings from clinical trials and research studies spanning various dementia types and utilizing multiple neurological and peripheral matrices using data derived from our SomaScan® Platform. Their discoveries inspire us and are proof that forward momentum is being made – as a consequence to high-throughput proteomics - to better understand this group of diseases and identify meaningful therapuetics .

Learn more

BlogProteomic profiling for discovery of biomarkers and mechanistic insights into acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow that is characterized by the abnormal proliferation of immature myeloid cells. It is the most common type of leukemia among the adult population that accounts for about 80% of all cases1. AML is a complex, genetically heterogeneous disease, which presents challenges for treatment. Although most patients respond to standard intensive chemotherapy, approximately two-thirds of the patients relapse within 18 months to 5 years of the initial treatment2. The bone marrow microenvironment is thought to play a significant role in mediating the persistence of malignant leukemic stem cells. However, the exact nature of bone marrow–leukemic cell interactions is not well understood.

Learn more

Explore blogs in our interactive viewer