ArticleAlzheimer's research & therapy2022
Eicosanoid lipidome activation in post-mortem brain tissues of individuals with APOE4 and Alzheimer's dementia.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
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- Lipid metabolism, neuroinflammation, and oxidative stress in Alzheimer disease: an integrated mechanistic review.Acta neurologica Belgica · 2026Review
- Oxylipin composition of high-density lipoprotein is altered in men and Hispanic adults with mild cognitive impairment.Journal of lipid research · 2026Article
- A perspective: PLA2G4A as drug target for vascular inflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Evidence for cPLA2 activation in Alzheimer's disease synaptic pathology.Acta neuropathologica communications · 2026Article
- Metabolic alteration in oxylipins and endocannabinoids point to an important role for soluble epoxide hydrolase and inflammation in Alzheimer's disease-finding from Alzheimer's Disease Neuroimaging Initiative.Alzheimer's research & therapy · 2026Article
- Development of potent, selective cPLAnpj drug discovery · 2026Article
- Long-chain polyunsaturated fatty acid lipid and oxylipin alterations in postoperative delirium after cardiac surgery.Journal of lipid research · 2026Article
- Ion Mobility-Mass Spectrometry Imaging: Advances in Biomedical Research.Biotech (Basel (Switzerland)) · 2025Review
- The role of fatty acids in neurodegenerative diseases: mechanistic insights and therapeutic strategies.Journal of lipid research · 2025Review
- Polyunsaturated fatty acids, APOE genotypes, and dementia incidence and mortality among hypertensive adults.The journal of prevention of Alzheimer's disease · 2025Article
- Air pollution and Alzheimer disease phenotype deplete esterified proresolving lipid mediator reserves in the brain.JCI insight · 2025Article
- Country-level incidence of Alzheimer disease and related dementias is associated with increased omega-6-PUFA consumption.Communications medicine · 2025Article
- Sleep Deprivation and Alzheimer's Disease: A Review of the Bidirectional Interactions and Therapeutic Potential of Omega-3.Brain sciences · 2025Review
- Inhibition of soluble epoxide hydrolase confers neuroprotection and restores microglial homeostasis in a tauopathy mouse model.Molecular neurodegeneration · 2025Article
- Lipid mediators in post-mortem brain samples from patients with Alzheimer's disease: A systematic review.Brain, behavior, & immunity - health · 2025Review
- Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.Antioxidants & redox signaling · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic neuroinflammation is one of the hallmarks of late-onset Alzheimer's disease (AD) dementia pathogenesis. Carrying the apolipoprotein ε4 (APOE4) allele has been associated with an accentuated response to brain inflammation and increases the risk of AD dementia progression. Among inflammation signaling pathways, aberrant eicosanoid activation plays a prominent role in neurodegeneration.
methodsUsing brains from the Religious Order Study (ROS), this study compared measures of brain eicosanoid lipidome in older persons with AD dementia to age-matched controls with no cognitive impairment (NCI), stratified by APOE genotype.
resultsLipidomic analysis of the dorsolateral prefrontal cortex demonstrated lower levels of omega-3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and DHA-derived neuroprotectin D1 (NPD-1) in persons with AD dementia, all of which associated with lower measures of cognitive function. A significant interaction was observed between carrying the APOE4 allele and higher levels of both pro-inflammatory lipids and pro-resolving eicosanoid lipids on measures of cognitive performance and on neuritic plaque burden. Furthermore, analysis of lipid metabolism pathways implicated activation of calcium-dependent phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and soluble epoxide hydrolase (sEH) enzymes.
conclusionThese findings implicate activation of the eicosanoid lipidome in the chronic unresolved state of inflammation in AD dementia, which is increased in carriers of the APOE4 allele, and identify potential therapeutic targets for resolving this chronic inflammatory state.
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