ArticleNeurotoxicity research2019
Development of a Human APOE Knock-in Mouse Model for Study of Cognitive Function After Cancer Chemotherapy.
Article in Neurotoxicity research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Influence of ApoE genotype on doxorubicin-induced cognitive impairment in juvenile rats.Scientific reports · 2025Article
- Alzheimer disease-related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study.Journal of the National Cancer Institute · 2024Article
- Constituents, pharmacological activities, pharmacokinetic studies, clinical applications, and safety profile on the classical prescription Kaixinsan.Frontiers in pharmacology · 2024Review
- Impact of exercise on cancer: mechanistic perspectives and new insights.Frontiers in immunology · 2024Review
- The chemotherapeutic agent doxorubicin induces brain senescence, with modulation by APOE genotype.Experimental neurology · 2024Article
- Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.Journal of geriatric oncology · 2023Article
- Behavioral and biologic characteristics of cancer-related cognitive impairment biotypes.Brain imaging and behavior · 2023Article
- Chemobrain: An accelerated aging process linking adenosine AInternational review of neurobiology · 2023Review
- Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE.Neurobiology of disease · 2022Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Independent APOE4 knock-in mouse models display reduced brain APOE protein, altered neuroinflammation, and simplification of dendritic spines.Journal of neurochemistry · 2022Article
- Chemobrain in Breast Cancer: Mechanisms, Clinical Manifestations, and Potential Interventions.Drug safety · 2022Review
- Mechanisms of Chemotherapy-Induced Neurotoxicity.Frontiers in pharmacology · 2022Review
- Animal models of chemotherapy-induced cognitive decline in preclinical drug development.Psychopharmacology · 2021Review
- Protective Effects ofJNCI cancer spectrum · 2021Article
- The association of genetic polymorphisms with neuroconnectivity in breast cancer patients.Scientific reports · 2021Article
- Breast Cancer, Alzheimer's Disease, andJournal of Alzheimer's disease reports · 2021Article
- Cancer Chemotherapy Related Cognitive Impairment and the Impact of the Alzheimer's Disease Risk FactorCancers · 2020Review
- A mouse model of chemotherapy-related cognitive impairments integrating the risk factors of aging and APOE4 genotype.Behavioural brain research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cancer-related cognitive impairment in breast cancer patients exposed to multi-agent chemotherapy regimens is associated with the apolipoprotein E4 (APOE4) allele. However, it is difficult to determine the effects of specific agents on cognitive impairment in human studies. We describe the development of a human APOE knock-in congenic C57BL/6J mouse model to study cancer-related cognitive impairment. Female APOE3 and APOE4 homozygous mice were either left untreated or treated with the most commonly used breast cancer therapeutic agent, doxorubicin. APOE3 and APOE4 mice had similar behaviors in exploratory and anxiety assays, which were affected transiently by doxorubicin treatment. Spatial learning and memory were measured in a Barnes maze: after 4 days of training, control APOE3 and APOE4 mice were able to escape with similar latencies. In contrast, doxorubicin-treated APOE4 mice had markedly impaired learning compared to doxorubicin-treated APOE3 mice at all time points. Voxel-based morphometry of magnetic resonance images revealed that doxorubicin treatment caused significant changes in the cortex and hippocampus of in both APOE3 and APOE4 mouse brains, but the differences were significantly greater in the APOE4 brains. The results indicate that doxorubicin-exposed APOE4 mice recapitulate key aspects of human cancer-related cognitive impairment. These data support the usefulness of this novel preclinical model for future elucidation of the genetic and molecular interactions of APOE genotype with chemotherapy; this model can also allow extension to prospective studies of older mice to study these interactions in the context of aging.
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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.