Neuroinflammation Dynamics in Alzheimer’s Disease

Alzheimer’s disease is characterised not only by the accumulation of amyloid-β plaques and tau tangles but also by a complex interplay of inflammatory processes that evolve over the course of the illness. Neuroinflammation involves the activation of microglia and astrocytes, the release of cytokines and chemokines, disruption of the blood–brain barrier and infiltration of peripheral immune cells. In early stages, acute inflammatory signalling may aid in the clearance of protein aggregates, whereas chronic activation fosters a self-sustaining cycle of tissue damage, synaptic loss and neuronal death. A failure of normal resolution pathways—those that should terminate inflammation and restore homeostasis—contributes to persistent glial activation, oxidative stress and impaired clearance of toxic proteins. Recent evidence has highlighted metabolic, genetic and lifestyle factors that modulate this inflammatory milieu, underscoring the global significance of neuroinflammation as both a biomarker and a therapeutic target.

Research from Nature Portfolio

Recent studies have revealed that neuronal expression of sphingosine kinase 1 (SphK1) plays a crucial role in regulating inflammation resolution. In Alzheimer’s models, reduction of SphK1 in neurons led to diminished secretion of specialised pro-resolving mediators (SPMs) and defective microglial phagocytosis of amyloid-β. Restoration of neuronal SphK1 levels promoted acetylation of cyclooxygenase 2, enhanced production of SPMs such as 15-R-lipoxin A4 and ameliorated pathology and cognitive deficits. These findings uncover a novel mechanism by which neuronal lipid signalling governs microglial function and suggest that boosting SphK1 activity may offer a strategy to resolve chronic neuroinflammation in Alzheimer’s disease.

Neuroinflammation Dynamics in Alzheimer’s Disease publication trend

The graph below shows the total number of articles in neuroinflammation dynamics in alzheimer’s disease across all publications each year (not limited to Nature Index journals).

Technical terms

Amyloid-β: Peptide fragments that aggregate extracellularly to form plaques characteristic of Alzheimer’s pathology.

Tau protein: Microtubule-associated protein that, when hyperphosphorylated, forms neurofibrillary tangles within neurons.

Microglia: Resident immune cells of the central nervous system that mediate surveillance, phagocytosis and cytokine production.

Neutrophils: Innate immune cells that can infiltrate the brain, release proteases and oxidants, and form extracellular traps.

Specialised pro-resolving mediators (SPMs): Lipid derivatives, often from omega-3 fatty acids, that actively terminate inflammation and promote tissue repair.

Blood–brain barrier: A selective vascular interface that regulates the entry of cells and molecules into the central nervous system.

References

1. Role of neuroinflammation in neurodegeneration development. Signal Transduction and Targeted Therapy (2023).
2. Impaired Resolution of Inflammation in Alzheimer’s Disease: A Review. Frontiers in Immunology (2017).
3. Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in a model of Alzheimer’s Disease. Nature Communications (2018).
4. Aging, sex, metabolic and life experience factors: Contributions to neuro-inflammaging in Alzheimer’s disease research. Neuroscience & Biobehavioral Reviews (2024).
5. Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer’s disease. Acta Neuropathologica Communications (2022).