Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus
Open accessAbstract
The low-density lipoprotein receptor (LDLR) is the first described receptor for apolipoprotein E (apoE). We hypothesize that the absence of the LDLR, similar to the absence of apoE, results in impaired learning and memory processes. Six-month-old homozygous Ldlr-/- and wild-type littermates (Ldlr+/+), maintained on a standard lab chow diet, were used. Unlike humans, Ldlr-/- mice, under these conditions, do not develop atherosclerosis. The results of the Morris water escape task revealed an impaired spatial memory in the Ldlr-/- mice in comparison with Ldlr+/+ mice. Also in a T-maze task, the working memory performance of the Ldlr-/- mice was impaired. Furthermore, Ldlr-/- mice, in comparison with Ldlr+/+ mice, display a decreased number of synaptophysin-immunoreactive presynaptic boutons in the hippocampus CA1. In conclusion, the results show in mice deficiency for the LDLR results in impaired hippocampal-dependent memory functions. A decrease in the number of presynaptic boutons may underlay these behavioral alterations. Therefore, the LDLR may be an important receptor for apoE in the central nervous system.
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Ldlr−/− mice manifest substantial cognitive and behavioral impairments, including age-related deterioration of spatial and working memory, due to synaptic loss and reduced neurogenesis in the brain.
“Ldlr–/– mice manifest substantial cognitive and behavioral impairments, including age-related deterioration of spatial and working memory, due to synaptic loss and reduced neurogenesis in the brain.”
From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [17]
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BackgroundMulder, M., Blokland, A., van den Berg, D.-J., Schulten, H., Bakker, A. H. F., Terwel, D., Honig, W., de Kloet, E. R., Havekes, L. M., Steinbusch, H. W. M., et al. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780307 · Cited by 74 · see citing works
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Functional Roles of the Interaction of APP and Lipoprotein Receptors
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“…and decreased expression of the presynaptic protein synaptophysin and synaptic integrity in both hippocampal and dentate gyrus, with consequent impairment of spatial cognition [80], reduced hippocampal cell proliferation and synapses formation [81], and signs of impaired learning and memory [82].”
Hsu, C.-H., Chu, P.-W., Chen, Y.-Y., Ho, M.-H., Liao, E.-C., & Chen, S.-K. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04842-3
- Authors
- Mulder, M., Jansen, P. J., Janssen, B. J. A., van de Berg, W. D. J., van der Boom, H., Havekes, L. M., de Kloet, R. E., Ramaekers, F. C. S., & Blokland, A.
- Affiliations
- Maastricht University Medical Centre (NL)
- Leiden University (NL)
- Corresponding author
- Mulder, Monique
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 16
- Issue
- 1
- Pages
- 212-219
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2114597265
- Cited by
- 98
- References
- 7
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 3
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- TNO Repository (submittedVersion)
- Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Internationale Stichting Alzheimer Onderzoek (98505)
- Hersenstichting
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- LDL receptor, apolipoprotein E, spatial memory, working memory, hippocampus, synaptic density, presynaptic terminals, synaptophysin, Ldlr knockout mice, hippocampal-dependent memory, learning and memory impairment
- MeSH terms
- Animals, Cell Count, Hippocampus, Male, Memory Disorders, Mice, Inbred C57BL, Receptors, LDL, Synapses, Presynaptic Terminals, Mice, Knockout, Maze Learning, Mice
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