Next-generation brain proteomics: Integrating single-cell, spatial, and multi-omics for clinical biomarker discovery

Area of Science:

• Neuroscience
• Proteomics
• Biochemistry

Background:

• The mammalian brain's complexity relies on neuronal and glial architecture, governed by its dynamic proteome.
• Understanding neural computation and disease mechanisms requires detailed proteomic insights.

Purpose of the Study:

• To review technological advancements in neuroproteomics, from bulk tissue analysis to single-cell and spatial resolutions.
• To examine how new platforms enhance phenotypic profiling of limited brain samples.
• To discuss the clinical translation of neuroproteomic findings for precision medicine.

Main Methods:

• Integration of next-generation neuroproteomic platforms (e.g., TIMS-PASEF, Orbitrap-Astral).
• Analysis of proteomic remodelling in lineage specification and synaptic plasticity.
• Verification of aberrant proteomic signatures in cerebrospinal fluid (CSF) and plasma.

Main Results:

• Next-generation platforms offer deeper, faster profiling of small brain samples.
• Proteomic studies reveal temporal protein expression linked to biological functions.
• Challenges include dynamic range limitations, sample loss, and detection of low-abundance proteins.

Conclusions:

• Despite limitations, neuroproteomics provides critical insights into brain function and disease.
• Clinical validation in CSF and plasma supports precision medicine applications.
• Fused multi-omics and AI are essential for decoding brain pathology's molecular logic.