According to the National Center for Advancing Translational Sciences at NIH, “translational science is the field that generates scientific and operational innovations that overcome longstanding challenges along the translational research pipeline.” The translational science spectrum describes the [nonlinear] stages of translational research: 

• Basic research 

• Preclinical research 

• Clinical research 

• Clinical implementation 

• Public health 

In this context, how can a fully automated, multiplexed proteomic platform with industry-leading sensitivity and dynamic range impact translational science?  

The Translational Science Spectrum (credit: NCATS @ NIH) 

Clinical research: Dynamic changes in plasma biomarkers in people treated with lecanemab 

Anti-amyloid monoclonal antibody therapies that clear amyloid in the brain and slow cognitive and functional decline are now approved for patients with mild AD. Identifying patients with early AD is achieved through amyloid-PET imaging, cerebrospinal fluid (CSF) Aβ42 and phosphorylated tau markers, and recently, the blood-based Aβ42-to-pTau-217 ratio. However, many useful pharmacological biomarkers are still missing. For example, there are no pharmacodynamic markers that indicate when a person can stop anti-amyloid therapy.  

Cruchaga is studying the plasma proteomic effects of the first of these therapies, lecanemab, to identify biomarkers that predict changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB), a clinical assessment of cognition and function. The NULISAseq CNS Disease Panel 120 “encompasses many pathways” that underlie AD progression and, presumably, response to therapy. The longitudinal clinical cohort being studied includes age-matched controls, placebo-treated patients with AD, and 287 individuals treated or expected to receive (pre-initiated) lecanemab, ranging from zero to several infusions over 96 weeks.    

Unpublished results show that plotting the effect-size changes of CNS Disease Panel proteins reveals which proteins contribute to the disease signature, and cycling through different time points creates a “molecular movie” of changes driven by lecanemab. Several proteins of interest, including the key marker pTau-217, normalize to control levels over multiple infusions. Paradoxically, amyloid peptide levels seem to “over-correct,” continuing their trajectories past control levels with additional infusions. Other proteins, such as TREM2 and oligo-SNCA, become more dysregulated. Although these results need validation in additional cohorts, the data offer a rich source of potential biomarkers to better understand AD pathology and treatment response. 

Basic research & public health of traumatic brain injury: “The status quo is rubbish” 

While the pathological changes in neurodegenerative diseases like AD develop gradually over decades, traumatic brain injuries (TBI) begin with a “single biomechanical insult event that triggers a cascade of brain changes,” according to Imperial College London Professor Dr. David Sharp. Beyond the immediate cognitive and functional loss after injury, TBI predisposes victims to epilepsy, movement disorders, migraines, and dementias, including AD. Globally, TBI is an annual $400 billion issue affecting 50-60 million people, especially younger individuals. 

Dr. Sharp promotes a more mechanistic understanding of the brain. Cellular (neuronal, astrocytic, and microglial) and pathological (amyloid/tau, TDP-43, blood-brain barrier disruption, autophagy, and synaptic dysfunction) biomarkers should enhance injury characterization and improve clinical utility. 

When a person with potential TBI is admitted to a medical facility, triage focuses on determining whether surgery is necessary. To decide if a patient needs a computerized tomography (CT) scan, the FDA has approved blood tests for glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1). While these tests help lower costs associated with unnecessary CT scans, they provide limited information about the underlying biology or the future risk of neurodegeneration and can sometimes lead to misdiagnosing a severe TBI.    

“The status quo is rubbish and needs improvement,” Dr.. Sharp observes. His team uses NULISA to identify novel biomarkers that aid in screening (diagnosis and prognosis), triage (risk assessment), and monitoring of TBI patients (disease progression and therapeutic response), as evidenced by Dr. Sharp’s recent publication and our accompanying blog on TBI biomarkers ​(Li et al., 2024)​. The NULISAseq CNS Disease Panel 120 contains the essential ingredients for translational biomarker evaluation, such as: 

• Well-characterized markers (e.g., UCHL1 and GFAP)  

• Markers of cell dysfunction: UCHL1 for neuronal injury, GFAP for astrocyte activation, and TREM2 for microglial activation 

• Pathological mechanisms: amyloid, tau, & TDP-43; NEFL for BBB disruption; SQSTM1 for autophagy (a novel direction); and SNAP25 for synaptic dysfunction 

• Associations with neuroimaging: biomarkers may explain the pathology underpinning diffuse axonal injury (i.e., water in the brain imaged with MRI)

Clinical implementation: Monitoring and evaluating sport-related TBI 

Since many individuals contract TBI as a result of contact sports injuries, Dr. Sharp has partnered with the Rugby Football Union and Premiership Rugby through the Institute of Sport, Exercise and Health in London to evaluate the brain health of retired elite rugby players.  

“We don’t understand the relationship between biomechanics and biochemistry,” Dr. Sharp explains. “This research can inform better protection for players and when to leave the field after severe contact occurs.” 

To improve biomechanics monitoring, professional rugby union players use instrumented mouthguards (iMGs) embedded with sensors that continuously measure acceleration, providing data on the magnitude of head impacts. Dr. Sharp aims to correlate iMG data with blood microsampling collected before and after matches to identify biomarkers that change immediately after a triggering TBI.  

NULISA is well-suited to deliver the proteomic readout. In a recent publication, Dr. Sharp and colleagues identified specific plasma biomarker changes in mid-life retired elite rugby players, including decreased GFAP and SNAP25 in ex-forwards, who participate in the most intense contact. Elevated pTau-181 was also observed in ex-forwards, indicating non-AD-related tau pathology ​(Graham et al., 2025)​. Although these players retired before the advent of iMGs, it’s intriguing to speculate on the striking results (pun intended) that combining continuous digital and blood-based biomarkers could reveal in contact sports and TBI.   

Preclinical: Mighty mouse model markers 

Aligning preclinical mouse and rodent models with human biomarker studies allows researchers to identify specific pathways and mechanisms behind disease. Reverse translational research provides precise control over variables, helps recreate both acute and long-term outcomes within a reasonable timeframe, and enables the investigation of tissues and biofluids that can’t be studied in humans. 

Earlier this year, Alamar launched the NULISAseq Mouse Panel 120, which encompasses the mouse-specific cytokines, growth factors, and CNS proteins that inform on neuroinflammation and neurodegeneration. The panel shows robust performance (median intra-assay CV of 5%) and over 95% detectability in mouse plasma, even with just 5 μl of input volume. Mouse plasma from models of amyloid pathology, tau pathology, and ApoE4-associated AD, as well as mouse brain extracts from a TBI model, all recapitulate expected protein signatures compared to controls (see our poster from ADPD).  

The Mouse Panel has translational potential beyond CNS diseases. In a recent preprint, Dr. David Lefer and colleagues at Cedars-Sinai used the Mouse Panel to explore whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can protect against heart failure with preserved ejection fraction (HFpEF) independently of weight loss. By using low-dose semaglutide to distinguish weight loss effects from other biochemical factors, the team identified signatures of reduced cardiovascular fibrosis and systemic inflammation (e.g., IL11, IFNγ, and IL-17B), along with improved vascular and diastolic function (e.g., DLL1, TREM2, and TNFRSF11B) ​(Elbatreek et al., 2025)​.  

Controlling environmental variables and utilizing multiplexed, ultra-high-sensitivity NULISA in mouse models allowed for the dissection of mechanisms that could guide future clinical applications.  

Tool for Translation 

For researchers aiming to broadly advance translational science, the NULISA platform checks many boxes. Carefully curated multiplexing with the highest available sensitivity across various sample types enhances research at every stage. Hands-free automation and intuitive bioinformatics workflows facilitate clinical implementation. Empowering innovative, patient-centered scientists with these tools can greatly improve public health by enabling the development of translatable protein biomarkers.