ArticleJournal of neuropathology and experimental neurology2022
Apolipoprotein E ε4 Mediates Myelin Breakdown by Targeting Oligodendrocytes in Sporadic Alzheimer Disease.
Article in Journal of neuropathology and experimental neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Differential effects of environmental enrichment and physical exercise on glial biology in aging and aging-related conditions: a systematic review.Frontiers in cellular neuroscience · 2026Pooled it
- Longitudinal changes in control energy of brain networks in older adults at familial risk for Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Review
- White Matter Microstructural Alterations Mediate the Association between Polygenic Risk for Alzheimer's Disease and Cognitive Performance in Clinically Asymptomatic Adults.Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2026Article
- Spatially resolved transcriptome-metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer's pathology.bioRxiv : the preprint server for biology · 2026Article
- Article
- Potential Role of Red Yeast Rice in the Prevention and Treatment of Alzheimer's Disease.International journal of medical sciences · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Emerging Role of Oligodendrocytes Malfunction in the Progression of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- How do different cell populations orchestrate myelin regeneration?Biochemical Society transactions · 2025Review
- The Role of Oligodendrocytes in Neurodegenerative Diseases: Unwrapping the Layers.International journal of molecular sciences · 2025Review
- APOE genotype determines cell-type-specific pathological landscape of Alzheimer's disease.Neuron · 2025Article
- Human longevity and Alzheimer's disease variants act via microglia and oligodendrocyte gene networks.Brain : a journal of neurology · 2025Article
- Oligodendrocytes in Alzheimer's disease pathophysiology.Nature neuroscience · 2025Review
- APOEε4 alters ApoE and Fabp7 in frontal cortex white matter in prodromal Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.Brain communications · 2025Article
- Physical Exercise Counteracts Aging-Associated White Matter Demyelination Causing Cognitive Decline.Aging and disease · 2024Review
- Cardiac Autonomic Neuropathy Is Not Associated with Apolipoprotein E Gene Isoforms in the Kazakh Population: A Case-Control Study.Diagnostics (Basel, Switzerland) · 2024Article
- Testing the structural disconnection hypothesis: Myelin content correlates with memory in healthy aging.Neurobiology of aging · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
White matter degradation in the frontal lobe is one of the earliest detectable changes in aging and Alzheimer disease. The ε4 allele of apolipoprotein E (APOE4) is strongly associated with such myelin pathology but the underlying cellular mechanisms remain obscure. We hypothesized that, as a lipid transporter, APOE4 directly triggers pathology in the cholesterol-rich myelin sheath independent of AD pathology. To test this, we performed immunohistochemistry on brain tissues from healthy controls, sporadic, and familial Alzheimer disease subjects. While myelin basic protein expression was largely unchanged, in frontal cortex the number of oligodendrocytes (OLs) was significantly reduced in APOE4 brains independent of their Braak stage or NIA-RI criteria. This high vulnerability of OLs was confirmed in humanized APOE3 or APOE4 transgenic mice. A gradual decline of OL numbers was found in the aging brain without associated neuronal loss. Importantly, the application of lipidated human APOE4, but not APOE3, proteins significantly reduced the formation of myelinating OL in primary cell culture derived from Apoe-knockout mice, especially in cholesterol-depleted conditions. Our findings suggest that the disruption of myelination in APOE4 carriers may represent a direct OL pathology, rather than an indirect consequence of amyloid plaque formation or neuronal loss.
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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.