ArticleThe Journal of biological chemistry2011
Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 214 citations in OpenAlex.
- Docosahexaenoic acid supplementation in age-related cognitive decline: a systematic review and meta-analysis.European journal of clinical pharmacology · 2020Pooled it
- Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2019Pooled it
- Characterization of Metabolites in Plasma, Urine and Feces of Healthy Participants after Taking Brahmi Essence for Twelve Weeks Using LC-ESI-QTOF-MS Metabolomic Approach.Molecules (Basel, Switzerland) · 2021Trial
- Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial.EBioMedicine · 2020Trial
- Omega-3 Fatty Acids and Alzheimer's Disease: Toward a New Understanding of Neuroprotective Mechanisms and Intervention Strategies.Marine drugs · 2026Review
- Fatty Acids in Cancer Therapy: Chemical Conjugates, Nanocarriers, and Therapeutic Opportunities.Molecules (Basel, Switzerland) · 2026Review
- Lipidomic signatures reveal biomarkers of mild cognitive impairment.Translational psychiatry · 2026Article
- Cetoleic acid and other long-chain unsaturated fatty acids as neuroprotective nutraceuticals.Lipids in health and disease · 2026Review
- Causal Effect of Dietary Patterns on Cerebral Small Vessel Disease: A Mendelian Randomization Study.Food science & nutrition · 2026Article
- Introduction of Cistanche phelypaea fatty acids as a new natural neurotrophic supplement by evaluating its effects in normal and Alzheimer's diseased rats.Scientific reports · 2025Article
- Neuronal Count, Brain Injury, and Sustained Cognitive Function in 5×FAD Alzheimer's Disease Mice Fed DHA-Enriched Diets.Biomolecules · 2025Article
- Neuroprotective Role of Omega-3 Fatty Acids: Fighting Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Review
- Acetylcholinesterase Inhibition and Antioxidant Activity of DHA-Disubstituted Phospholipids.Molecular nutrition & food research · 2025Article
- Lifestyle factors and plasma biomarkers of Alzheimer's disease: A narrative review.The journal of prevention of Alzheimer's disease · 2025Review
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- How Membrane Phospholipids Containing Long-Chain Polyunsaturated Fatty Acids and Their Oxidation Products Orchestrate Lipid Raft Dynamics to Control Inflammation.The Journal of nutrition · 2024Review
- Effects of APOE4 on omega-3 brain metabolism across the lifespan.Trends in endocrinology and metabolism: TEM · 2024Review
- Spatially and temporally probing distinctive glycerophospholipid alterations in Alzheimer's disease mouse brain via high-resolution ion mobility-enabled sn-position resolved lipidomics.Nature communications · 2024Article
- Increasing the Survival of a Neuronal Model of Alzheimer's Disease Using Docosahexaenoic Acid, Restoring Endolysosomal Functioning by Modifying the Interactions between the Membrane Proteins C99 and Rab5.International journal of molecular sciences · 2024Article
- Novel insights into brain lipid metabolism in Alzheimer's disease: Oligodendrocytes and white matter abnormalities.FEBS open bio · 2024Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.