ArticleMolecular psychiatry2022
Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Deciphering the peripheral immune landscape of Alzheimer's disease through integrated multi-omics research and cohort validation.Frontiers in immunology · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- APOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia.Annals of clinical and translational neurology · 2025Article
- Pathways to Alzheimer's Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-β Regulation and Neuronal Health.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Review
- Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Association of whole-person eigen-polygenic risk scores with Alzheimer's disease.Human molecular genetics · 2024Article
- Elderly mice with history of acetaminophen intoxication display worsened cognitive impairment and persistent elevation of astrocyte and microglia burden.Scientific reports · 2024Article
- Silencing Apoe with divalent-siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Article
- Gastrointestinal Dysfunction in Neurological and Neurodegenerative Disorders.Seminars in neurology · 2023Review
- Plasma apolipoprotein E levels, isoform composition, and dimer profile in relation to plasma lipids in racially diverse patients with Alzheimer's disease and mild cognitive impairment.Alzheimer's research & therapy · 2023Article
- Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus.PLoS pathogens · 2023Article
- Peripheral apolipoprotein E proteins and their binding to LRP1 antagonize Alzheimer's disease pathogenesis in the brain during peripheral chronic inflammation.Neurobiology of aging · 2023Article
- Behavioral and cognitive performance of humanized APOEε3/ε3 liver mice in relation to plasma apolipoprotein E levels.Scientific reports · 2023Article
- Alzheimer's disease: targeting the peripheral circulation.Molecular neurodegeneration · 2023Article
- Ranking the risk factors for Alzheimer's disease; findings from the UK Biobank study.Aging brain · 2023Article
- The APOE-TOMM40 Humanized Mouse Model: Characterization of Age, Sex, and PolyT Variant Effects on Gene Expression.Journal of Alzheimer's disease : JAD · 2023Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer's disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah-/-, Rag2-/-, Il2rg-/- mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
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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 Socratic graph.