Neuroinflammation in Alzheimer’s disease: pathogenic signaling, biomarkers, and emerging therapeutic interventions
8 affiliations
- 1Sachdeva College of Pharmacy
- 2Desh Bhagat University
- 3Rayat Bahra Institute of Pharmacy
- 4Gautam College of Pharmacy
- 5Faculty of Pharmaceutical Sciences, The ICFAI University Baddi
- 6M.M College of Pharmacy, MM(DU)
- 7L.R. Institute of Pharmacy, Jabli-kyar, Oachaghat
- 8National Institute of Pharmaceutical Education and Research (NIPER)
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia worldwide, characterized by progressive cognitive decline and neurodegeneration. Although amyloid-β plaques and hyperphosphorylated tau are major pathological hallmarks, increasing evidence highlights persistent neuroinflammation as a critical contributor to disease progression. Activated microglia and astrocytes, inflammatory cytokines, inflammasome activation, and dysregulated immune responses promote neuronal damage and synaptic dysfunction. Similar inflammatory mechanisms are observed in neurological disorders such as multiple sclerosis (MS) and brain tumors, suggesting shared molecular pathways linking neuroinflammation, neurodegeneration, and tumor-associated immune responses. Proteomics, transcriptomics, and multi-omics approaches provide powerful strategies to characterize disease-associated molecular signatures, signaling pathways, biomarkers, and therapeutic targets. This review summarizes key neuroinflammatory mechanisms in AD, including NF-κB, NLRP3, PI3K/Akt, MAPK, cGAS–STING, mitochondrial, lysosomal, calcium, insulin, and blood–brain barrier pathways. Recent advances in proteomic and transcriptomic profiling and their integration with genomic, epigenomic, and metabolomic data are discussed for understanding disease heterogeneity and identifying clinically relevant biomarkers. Current and emerging therapeutic strategies, including anti-Aβ antibodies, anti-inflammatory agents, selective inhibitors, dual-target compounds, PROTACs, and protein–protein interaction modulators, are also evaluated. Finally, multi-omics-based precision medicine and artificial intelligence-assisted analysis may facilitate biomarker-guided patient stratification and development of effective disease-modifying therapies.
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BibTeX
@article{poonam2026neuroinflammation,
title = {{Neuroinflammation in Alzheimer’s disease: pathogenic signaling, biomarkers, and emerging therapeutic interventions}},
author = {Poonam and Rekha Rana and Mohita Thakur and Aanchal Sharma and Shivani Pannu and Shivani Sharma and Subh Naman and Sapna Rani and Diksha Devi and Vishal Kumar and Sunny Kumar},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1908830},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1908830/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neuroinflammation in Alzheimer’s disease: pathogenic signaling, biomarkers, and emerging therapeutic interventions
AU - Poonam
AU - Rekha Rana
AU - Mohita Thakur
AU - Aanchal Sharma
AU - Shivani Pannu
AU - Shivani Sharma
AU - Subh Naman
AU - Sapna Rani
AU - Diksha Devi
AU - Vishal Kumar
AU - Sunny Kumar
PY - 2026
DA - 2026/10/23
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1908830
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1908830/full
AB - Alzheimer’s disease (AD) is the leading cause of dementia worldwide, characterized by progressive cognitive decline and neurodegeneration. Although amyloid-β plaques and hyperphosphorylated tau are major pathological hallmarks, increasing evidence highlights persistent neuroinflammation as a critical contributor to disease progression. Activated microglia and astrocytes, inflammatory cytokines, inflammasome activation, and dysregulated immune responses promote neuronal damage and synaptic dysfunction. Similar inflammatory mechanisms are observed in neurological disorders such as multiple sclerosis (MS) and brain tumors, suggesting shared molecular pathways linking neuroinflammation, neurodegeneration, and tumor-associated immune responses. Proteomics, transcriptomics, and multi-omics approaches provide powerful strategies to characterize disease-associated molecular signatures, signaling pathways, biomarkers, and therapeutic targets. This review summarizes key neuroinflammatory mechanisms in AD, including NF-κB, NLRP3, PI3K/Akt, MAPK, cGAS–STING, mitochondrial, lysosomal, calcium, insulin, and blood–brain barrier pathways. Recent advances in proteomic and transcriptomic profiling and their integration with genomic, epigenomic, and metabolomic data are discussed for understanding disease heterogeneity and identifying clinically relevant biomarkers. Current and emerging therapeutic strategies, including anti-Aβ antibodies, anti-inflammatory agents, selective inhibitors, dual-target compounds, PROTACs, and protein–protein interaction modulators, are also evaluated. Finally, multi-omics-based precision medicine and artificial intelligence-assisted analysis may facilitate biomarker-guided patient stratification and development of effective disease-modifying therapies.
SN - 2234-943X
ER -