Neuroinflammation and Oxidative Stress in Alzheimer's Disease

Alzheimer’s disease is characterised by progressive neuronal loss and cognitive decline, underpinned by two intertwined pathological processes: sustained neuroinflammation and excessive oxidative stress. Microglial cells and astrocytes respond to amyloid-β and tau pathology by releasing proinflammatory cytokines and reactive oxygen species, creating a chronic inflammatory milieu that perpetuates neuronal injury. Mitochondrial dysfunction exacerbates free-radical generation, impairing synaptic function and energy metabolism. Aβ oligomers and tau aggregates both elicit oxidative damage to lipids, proteins and DNA, while inflammation further disrupts blood–brain barrier integrity and recruits peripheral immune cells. This vicious cycle contributes to synaptic loss, neurotransmitter imbalance and ultimately brain atrophy. Understanding the interplay between these processes has revealed potential therapeutic targets, including antioxidant defence regulators and modulators of innate immune signalling, which may slow progression and ameliorate cognitive symptoms.

Research from Nature Portfolio

Recent work has delineated the neuroprotective capacity of vanillic acid in a model of Aβ1-42-induced pathology. Treatment was shown to enhance endogenous antioxidant defences by activating Nrf2 and haem oxygenase-1 via Akt and GSK-3β pathways, thereby restoring glutathione levels and curbing excessive reactive oxygen species. Concurrent reduction of proinflammatory mediators and preservation of synaptic markers translated to improved memory performance and neuronal survival, highlighting a promising small-molecule approach to interrupt the feed-forward loop of oxidative stress and inflammation in Alzheimer’s pathology.

Neuroinflammation and Oxidative Stress in Alzheimer's Disease publication trend

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

Technical terms

Neuroinflammation: Sustained activation of glial cells and immune pathways within the central nervous system in response to injury or pathology.

Oxidative stress: Imbalance between free-radical generation (reactive oxygen species) and antioxidant defences leading to molecular damage.

Microglia: Resident immune cells of the brain that detect and respond to pathological stimuli by releasing cytokines and reactive oxygen species.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can oxidise biomolecules and impair cellular function.

Nrf2 (nuclear factor erythroid 2-related factor 2): A transcription factor that regulates expression of antioxidant enzymes and cellular defence mechanisms against oxidative damage.

References

1. Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier. Ageing Research Reviews (2024).
2. Attenuation of amyloid‐β‐induced mitochondrial dysfunction by active components of anthocyanins in HT22 neuronal cells. MedComm (2023).
3. Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer’s disease: a randomized phase 1 study. BMC Medicine (2023).
4. Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice. Scientific Reports (2017).