ArticleEBioMedicine2015
White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04360148 (Randomized-controlled Study for Evaluation of Ketogenic Metabolic Nutritional Pattern in Subjects With High-frequency Episodic Migraine), which is not on this map. Cited by 118 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Randomized-controlled Study for Evaluation of Ketogenic Metabolic Nutritional Pattern in Subjects With High-frequency Episodic Migraine
Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2023Pooled it
- Report of the FDA's expert panel on hormone therapy.Menopause (New York, N.Y.) · 2026Review
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- Impact of Menopause and Menopausal Hormone Therapy on Liver-Kidney-Metabolic Health.Advances in therapy · 2026Review
- Parent-of-origin effects in Alzheimer's liability dissociate neurocognitive and cardiovascular traits in at-risk individuals.Cell reports. Medicine · 2026Article
- Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes.Nature communications · 2026Article
- High-fat diet is associated with accelerated gray matter atrophy in cognitively unimpaired older adults but slower atrophy in individuals with existing mild cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Plasma proteomics link menopause timing to brain aging and dementia risk.Research square · 2026Article
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- Plasma proteomics link menopause timing to brain aging and dementia risk.medRxiv : the preprint server for health sciences · 2026Article
- Meta analysis of glucose metabolism across Alzheimer's, Parkinson's and ALS Reveals emergence of adaptive brain glucometabolic responses and associated neurological functional profiles.medRxiv : the preprint server for health sciences · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Five energy metabolism pathways show distinct regional distributions and lifespan trajectories in the human brain.PLoS biology · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- BDH1-Dependent Ketone Body Metabolism Maintains Müller Cell Homeostasis and Retinal Function.bioRxiv : the preprint server for biology · 2025Article
- Oligodendrocyte lineage cells dysfunction in depression: early life stress, adolescent vulnerability and the emerging role of lipid metabolism.Translational psychiatry · 2025Review
- White matter microstructural and macrostructural profiles during midlife reveal sex differences between men and women at different menopausal stages.Scientific reports · 2025Article
- The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.Molecular and cellular biochemistry · 2025Review
- Interactions between menopause and high-fat diet on cognition and pathology in a mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
58 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
8 authors at 4 institutions in 1 country.
Funding
Abstract
White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.
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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.