Beyond a Single Biomarker: Exploring Neurological Disease with the NULISAseq™ Neuro 220 Panel

Neurological diseases rarely result from changes in a single protein or pathway. Conditions such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and traumatic brain injury can involve overlapping changes in protein aggregation, neuroinflammation, synaptic function, metabolism and neuronal integrity.

Established biomarkers provide valuable insights, but measuring them in isolation may not capture disease heterogeneity or the wider biological response.

The NULISAseq™ Neuro 220 Panel measures 220 CNS-relevant proteins simultaneously. At Altheome, this high-multiplex profiling is supported by targeted assays, custom assay development and downstream data interpretation, helping researchers move from broad discovery towards focused validation.

Neuro 220 at a glance

• 220 CNS-relevant protein biomarkers

• Approximately 25 µL sample input, depending on workflow

• Compatible with plasma, serum and cerebrospinal fluid

• Coverage across protein aggregation, neuroinflammation, synaptic biology, metabolism and neuronal injury

• Supported by targeted assays, custom assay development and optional downstream interpretation

Why are neurological biomarkers challenging?

Biomarkers such as neurofilament light chain, phosphorylated tau, GFAP and alpha-synuclein can answer important focused questions, but no single marker captures the full biological picture.

Neuronal injury may occur alongside immune activation, synaptic dysfunction, impaired protein clearance or vascular changes. These processes can vary between individuals with the same diagnosis and overlap across different neurological diseases.

Measurement presents another challenge. Many CNS-related proteins are present at very low concentrations in peripheral blood, where brain-derived signals may become diluted or difficult to distinguish from proteins produced elsewhere in the body. Cerebrospinal fluid can provide closer insight into CNS biology, but collection is more invasive and may be less practical for large cohorts or repeated sampling.

Ultra-sensitive, high-multiplex proteomics can help address these limitations by measuring multiple low-abundance biomarkers together.

What is the NULISAseq Neuro 220 Panel?

The Neuro 220 Panel measures proteins selected for their relevance to neurodegeneration, neuroinflammation and wider CNS biology. It expands the pathway depth of the earlier CNS 120 panel while retaining core neurologically relevant biomarkers.

NULISA combines antibody-based recognition with DNA barcoding and next-generation sequencing. When two target-specific antibodies bind the same protein, their DNA tags are brought together and amplified, enabling sensitive measurement across hundreds of targets.

The platform is particularly suited to discovery and pathway-level profiling, combining high multiplexing with sensitivity for low-abundance neurological and inflammatory biomarkers.

Its relatively small sample requirement may also be valuable for longitudinal studies, limited-volume clinical samples, biobank material and studies in which several analyses must be performed from the same specimen.

Looking beyond NfL and pTau

The panel includes established neurological biomarkers, but its value lies in placing them within a broader biological context.

Protein aggregation

The panel covers several major neurological proteinopathies, including multiple phosphorylated tau species, amyloid beta, alpha-synuclein, TDP-43 and APOE4.

Measuring these markers together may help researchers examine overlapping pathologies rather than focusing on one disease-associated protein in isolation.

Neuroinflammation and immune signalling

Markers including GFAP, YKL-40, TREM-2, IL-6 and NLRP3 provide insight into glial activation, cytokine signalling and innate immune responses.

This allows researchers to investigate whether changes in protein aggregation or neuronal injury occur alongside a wider inflammatory response.

Synaptic and neuronal function

SNAP-25, neurogranin, BDNF, GAP43 and NPTX2 provide coverage of synaptic function, neuronal survival and repair-related biology.

Proteostasis, metabolism and injury

NfL, UCHL1, GBA1, DJ-1 and FGF21 extend the analysis to axonal injury, protein clearance and mitochondrial or metabolic function.

Together, this pathway coverage helps researchers ask not only whether a recognised neurological biomarker has changed, but which other biological processes may accompany that change.

Where could the Neuro 220 Panel add value?

·        Biomarker discovery: Identify candidate proteins, multiprotein signatures and pathway-level responses without relying on a narrowly predefined target list.

·        Disease heterogeneity: Explore differences in protein aggregation, inflammation, synaptic dysfunction and neuronal injury within clinically similar groups.

·        Longitudinal profiling: Track how CNS-related biomarker patterns change during progression, recovery or treatment.

·        Target engagement and treatment response: Assess the intended pathway while detecting broader downstream biological effects.

The panel may therefore support studies in neurodegenerative disease, neuroinflammation, traumatic brain injury and other areas where several biological processes are likely to interact.

Turning high-multiplex data into meaningful insight

A 220-protein panel generates a rich dataset, but its value depends on study design and interpretation. Cohort size, matrix, sample handling, clinical variables and multiple testing should all be considered from the outset.

Candidate biomarkers should be assessed using a combination of detectability, effect size, inter-individual consistency and biological relevance - not statistical significance alone. The strongest findings can then be prioritised for validation in larger or independent cohorts.

From discovery to validation with Altheome

Altheome’s neuro offering does not end with the delivery of a high-multiplex dataset. Researchers are supported in identifying which findings should be prioritised and how they can be taken forward.

Candidates identified through Neuro 220 profiling can be evaluated using focused NULISA panels, ultra-sensitive singleplex assays or custom assay development. This allows a study to move from broad pathway-level discovery towards more targeted measurement of selected biomarkers.

Focused options include assays relevant to neurological disease, Alzheimer’s disease and traumatic brain injury, alongside singleplex assays for biomarkers such as NfL, tau and phosphorylated tau, GFAP, alpha-synuclein, SNAP-25, TDP-43, BDNF and amyloid beta.

Where a suitable assay is not already available, custom assay development can support novel targets, specific protein forms and emerging areas of CNS biology.

Support can also include study-design consultation, biomarker selection, sample and matrix recommendations, data generation, quality control and optional downstream analysis and interpretation.

Building a broader view of neurological disease

Established neurological biomarkers remain essential, but they represent only part of the underlying biology.

The NULISAseq Neuro 220 Panel enables researchers to examine protein aggregation, neuroinflammation, synaptic function, metabolism, vascular biology and neuronal injury within the same study.

Combined with Altheome’s targeted assays, complementary platforms, custom development and analytical support, the panel can form part of a complete neurological biomarker strategy - from broad discovery through to focused validation and longitudinal tracking.

Researchers planning a neurological biomarker study can speak with the Altheome scientific team to discuss their sample type, target biology and study objectives.