ArticleNature communications2018
Apoε4 disrupts neurovascular regulation and undermines white matter integrity and cognitive function.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
131 citing papers in PubMed, 3 syntheses or guidelines pooled it, 174 citations in OpenAlex.
- Impact of Apolipoprotein E4 on blood-brain barrier integrity in target replacement murine models: a systematic review and meta-analysis.Alzheimer's research & therapy · 2026Pooled it
- Dissecting the genetic and proteomic risk factors for delirium.Nature aging · 2026Pooled it
- The Role of Genetics in Stroke Risk and Outcome: A Review of Current Evidence.Brain and behavior · 2025Pooled it
- Theranostic Innovative Strategies for Brain Diseases: New Insights on Neurovascular Unit-Associated Pathological Changes in Neurodegenerative Disorders and Aging.International journal of molecular sciences · 2026Review
- A Quantitative Assessment of MRI-Visible Perivascular-Space Burden Across the Cognitive Spectrum: Associations with APOE ε4 Status and Venous Sinus Volume.Diagnostics (Basel, Switzerland) · 2026Article
- Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- White matter hyperintensities, cognitive decline and dementia risk in a community- dwelling cohort of northern Manhattan.Research square · 2026Article
- Dementia Risk in Type 1 and 2 Diabetes: A Nationwide Population-Based Comparison.Diabetes, obesity & metabolism · 2026Article
- Amyloid-related imaging abnormalities (ARIA) in anti-amyloid therapies for Alzheimer's disease: An update from the Alzheimer's Association ARIA workgroup.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- APOE ε4 carriage is associated with olfactory-hippocampal tract functional connectivity.Brain imaging and behavior · 2026Article
- Walking to protect against cognitive decline: the role of APOE genotype and sex.Biology of sex differences · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Counteracting white matter injury to mitigate APOE 𝜀4-related ARIA.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tregs Promote Astrocyte-Neuron Lactate Shuttle via Inhibiting STING Pathway to Improve Neurological Recovery After Ischemic Stroke.CNS neuroscience & therapeutics · 2026Article
- Microvascular dysfunction and aberrant network activity drive reduced brain oxygenation in a mouse tauopathy model.Research square · 2025Article
- Cortical layer multi-parameter analysis of neurovascular impairments in AD/ADRD rodent model with in vivo optical imaging.Translational neurodegeneration · 2025Article
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- The vascular contribution to cognitive decline in ageing and dementia.Nature reviews. Neuroscience · 2025Review
71 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 2 institutions in 1 country.
Funding
Abstract
The ApoE4 allele is associated with increased risk of small vessel disease, which is a cause of vascular cognitive impairment. Here, we report that mice with targeted replacement (TR) of the ApoE gene with human ApoE4 have reduced neocortical cerebral blood flow compared to ApoE3-TR mice, an effect due to reduced vascular density rather than slowing of microvascular red blood cell flow. Furthermore, homeostatic mechanisms matching local delivery of blood flow to brain activity are impaired in ApoE4-TR mice. In a model of cerebral hypoperfusion, these cerebrovascular alterations exacerbate damage to the white matter of the corpus callosum and worsen cognitive dysfunction. Using 3-photon microscopy we found that the increased white matter damage is linked to an enhanced reduction of microvascular flow resulting in local hypoxia. Such alterations may be responsible for the increased susceptibility to hypoxic-ischemic lesions in the subcortical white matter of individuals carrying the ApoE4 allele.
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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.