Integrating Neuroinflammation and Metabolomics to Decode Neurodegenerative Diseases: Mechanisms and Targeted Interventions

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, and related disorders, represent a major and growing global health challenge. Despite advances in genetics, neuropathology, and disease modeling, the mechanisms that initiate and sustain disease progression remain incompletely resolved, and truly disease-modifying therapies are still limited for most conditions. This translational gap underscores the need for mechanism-grounded biomarkers and therapeutically actionable targets that can improve early detection, risk stratification, and intervention timing.

Neurodegeneration is driven not by isolated pathways but by persistent neuroimmune and metabolic coupling across cellular ecosystems. Chronic activation of microglia and astrocytes reshapes cytokine networks, synaptic function, and blood-brain barrier homeostasis, while neurons and glia undergo coordinated shifts in bioenergetics, lipid turnover, mitochondrial function, and redox control. Metabolomics and lipidomics are uniquely positioned to quantify these dynamic states in biofluids, tissue, and model systems, thereby linking molecular mechanisms to clinically measurable phenotypes. Yet inflammation and metabolism are still often investigated separately, which weakens causal inference, limits cross-cohort reproducibility, and slows the development of patient-stratified therapies.

This Research Topic is designed to close the translational gap between mechanistic discovery and clinical application by integrating neuroinflammation with metabolomics across neurodegenerative disorders. We aim to build a coherent framework that links immune signaling, metabolic remodeling, and disease heterogeneity across molecular, cellular, circuit, and clinical scales. By emphasizing cross-platform reproducibility and biologically interpretable models, the Topic seeks to advance both mechanistic understanding and therapeutic development. We particularly encourage studies that combine metabolomic and lipidomic profiling with imaging, genetics, proteomics, and deeply phenotyped longitudinal cohorts.

Topics of interest include, but are not limited to:

• Immune-driven metabolic rewiring in neurodegeneration.
• CSF, blood, and tissue biomarkers for diagnosis and prognosis.
• Metabolite and lipid signatures of progression and treatment response.
• Causal and translational modeling using longitudinal multi-omics data.
• Clinical studies of immunometabolic therapies.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Neurodegenerative diseases, neuroinflammation, metabolomics, multi-omics integration, immunometabolism, microglia, astrocytes, lipidomics, biomarkers, precision medicine, targeted interventions

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.