ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Resting-state functional connectivity changes in aging apoE4 and apoE-KO mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 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
- A Deterministically Synchronized Widefield Imaging and Virtual Reality Platform for Multimodal Brain-Behavior Recording.bioRxiv : the preprint server for biology · 2026Article
- Traffic-Related Emissions Induce Angiotensin II-Dependent Oxidative Stress in the Hippocampus of ApoE-Null Male Mice.Antioxidants (Basel, Switzerland) · 2026Article
- Aging-dependent loss of functional connectivity in a mouse model of Alzheimer's disease and reversal by mGluR5 modulator.Molecular psychiatry · 2025Article
- Brain network fingerprints of Alzheimer's disease risk factors in mouse models with humanized APOE alleles.Magnetic resonance imaging · 2024Article
- Sex differences in interacting genetic and functional connectivity biomarkers in Alzheimer's disease.GeroScience · 2024Article
- APOE4 rat model of Alzheimer's disease: sex differences, genetic risk and diet.BMC neuroscience · 2024Article
- APOE, Immune Factors, Sex, and Diet Interact to Shape Brain Networks in Mouse Models of Aging.bioRxiv : the preprint server for biology · 2024Article
- Emerging Links between Cerebral Blood Flow Regulation and Cognitive Decline: A Role for Brain Microvascular Pericytes.Aging and disease · 2023Review
- The Preventive Effect of Exercise and Oral Branched-Chain Amino Acid Supplementation on Obesity-Induced Brain Changes in Ldlr-/-.Leiden Mice.Nutrients · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- APOE mediated neuroinflammation and neurodegeneration in Alzheimer's disease.Seminars in immunology · 2022Review
- Hippocampal functional connectivity across age in anFrontiers in aging neuroscience · 2022Article
- Vascular smooth muscle cell dysfunction in neurodegeneration.Frontiers in neuroscience · 2022Review
- Apolipoprotein E knockout may affect cognitive function in D-galactose-induced aging mice through the gut microbiota-brain axis.Frontiers in neuroscience · 2022Article
- Liuwei Dihuang Decoction Alleviates Cognitive Dysfunction in Mice With D-Galactose-Induced Aging by Regulating Lipid Metabolism and Oxidative StressFrontiers in neuroscience · 2022Article
- The gut microbiota modulates brain network connectivity under physiological conditions and after acute brain ischemia.iScience · 2021Article
- Emerging imaging methods to study whole-brain function in rodent models.Translational psychiatry · 2021Review
- Characterization of brain-wide somatosensory BOLD fMRI in mice under dexmedetomidine/isoflurane and ketamine/xylazine.Scientific reports · 2021Article
- Different posterior hippocampus and default mode network modulation in young APOE ε4 carriers: a functional connectome-informed phenotype longitudinal study.Molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well established that the cholesterol-transporter apolipoprotein ε (APOE) genotype is associated with the risk of developing neurodegenerative diseases. Recently, brain functional connectivity (FC) in apoE-ε4 carriers has been investigated by means of resting-state fMRI, showing a marked differentiation in several functional networks at different ages compared with carriers of other apoE isoforms. The causes of such hampered FC are not understood. We hypothesize that vascular function and synaptic repair processes, which are both impaired in carriers of ε4, are the major contributors to the loss of FC during aging. To test this hypothesis, we integrated several different MRI techniques with immunohistochemistry and investigated FC changes in relation with perfusion, diffusion, and synaptic density in apoE4 and apoE-knock-out (KO) mice at 12 (adult) and 18 months of age. Compared with wild-type mice, we detected FC deficits in both adult and old apoE4 and apoE-KO mice. In apoE4 mice, these changes occurred concomitant with increased mean diffusivity in the hippocampus, whereas perfusion deficits appear only later in life, together with reduced postsynaptic density levels. Instead, in apoE-KO mice FC deficits were mirrored by strongly reduced brain perfusion since adulthood. In conclusion, we provide new evidence for a relation between apoE and brain connectivity, possibly mediated by vascular risk factors and by the efficiency of APOE as synaptic modulator in the brain. Our results show that multimodal MR neuroimaging is an excellent tool to assess brain function and to investigate early neuropathology and aging effects in translational research.
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