Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although substantial research has been conducted to elucidate the complex pathophysiology of AD, the therapeutic approach still has limited efficacy in clinical practice. Oxidative stress (OS) has been established as an early driver of several age-related diseases, including neurodegeneration. In AD, increased levels of reactive oxygen species mediate neuronal lipid, protein, and nucleic acid peroxidation, mitochondrial dysfunction, synaptic damage, and inflammation. Thus, the identification of novel antioxidant molecules capable of detecting, preventing, and counteracting AD onset and progression is of the utmost importance. However, although several studies have been published, comprehensive and up-to-date overviews of the principal anti-AD agents harboring antioxidant properties remain scarce. In this narrative review, we summarize the role of vitamins, minerals, flavonoids, non-flavonoids, mitochondria-targeting molecules, organosulfur compounds, and carotenoids as non-enzymatic antioxidants with AD diagnostic, preventative, and therapeutic potential, thereby offering insights into the relationship between OS and neurodegeneration.

Background: Developing evidence highlight the importance of neuroinflammation in the progression of Alzheimer’s disease (AD) pathophysiology. It has been shown that inflammatory mechanisms affect both amyloid and tau deposition in the brain. However, given the complexity of the immune cascades and the unknown interactions between the peripheral and central nervous systems in the disease, it has been challenging to identify biomarkers that reflect a given inflammatory state in this context. Thus we aim here to further explore inflammation‐related proteins for potential biomarker utility in AD.Method: Participants from the TRIAD cohort incorporating within the AD spectrum, and with available TSPO PET ([¹¹C]PBR28) imaging data, had their cerebrospinal fluid (CSF) (n = 100) and plasma (n = 169) samples analyzed using Proximity Extension Assay (PEA) technology targeting 368 inflammation‐related proteins (Olink). LIMMA models evaluated the differential protein expression according to TSPO PET status (positivity attributed by 3 SD above the mean ROI‐SUVR of young participants), adjusting for age and brain amyloid load (PET). Associations were FDR corrected for multiple comparisons. Gene ontology (GO) was used for enrichment analysis on relevant results.Result: Preliminary results identified several proteins that are in higher concentration in the CSF of TSPO positive in comparison with TSPO negative participants (Figure 1). The enrichment analysis (Figure 2) unveiled terms related with cytokine and chemokine signaling pathways as well as with the regulation of mitogen‐activated protein kinase (MAPK) cascade, which is an interesting finding given the frequently reported association between MAPK cascade and AD.Conclusion: The initial assessment of the data revealed encouraging preliminary findings. However, more detailed analyses will be performed in both CSF and plasma to further investigate potential biomarkers and how they coverage between amyloid and tau deposition.