Apolipoprotein CI Knock-Out Mice Display Impaired Memory Functions

Berbée, Jimmy F.P.; Vanmierlo, Tim; Abildayeva, Karlygash; Blokland, Arjan; Jansen, Paula J.; Lütjohann, Dieter; Gautier, Thomas; Sijbrands, Eric; Prickaerts, Jos; Hadfoune, M'hamed; Ramaekers, Frans C.S.; Kuipers, Folkert; Rensen, Patrick C.N.; Mulder, Monique

doi:10.3233/jad-2010-100576

Cited by 25Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

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Apolipoprotein CI Knock-Out Mice Display Impaired Memory Functions

Berbée, Jimmy F.P., Vanmierlo, Tim, Abildayeva, Karlygash, Blokland, Arjan, Jansen, Paula J., Lütjohann, Dieter, Gautier, Thomas, Sijbrands, Eric, Prickaerts, Jos, Hadfoune, M'hamed, Ramaekers, Frans C.S., Kuipers, Folkert, Rensen, Patrick C.N., Mulder, Monique·2011·Journal of Alzheimer's Disease

DOI 10.3233/jad-2010-100576

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Abstract

The ε4 allele of apolipoprotein E (APOE4), which is a well established genetic risk factor for development of Alzheimer's disease (AD), is in genetic disequilibrium with the H2 allele of apolipoprotein C1 (APOC1), giving rise to increased expression of apoC-I. This raises the possibility that the H2 allele of APOC1, either alone or in combination with APOE4, provides a major risk factor for AD. In line herewith, we previously showed that mice overexpressing human APOC1 display impaired learning and memory functions. Here, we tested the hypothesis that the absence of Apoc1 expression in mice may improve memory functions. In contrast with our expectations, Apoc1(-/-) mice showed impaired hippocampal-dependent memory functions, as judged from their performance in the object recognition task (p < 0.001) as compared to their wild-type littermates. No gross changes in brain morphology or in brain sterol concentrations were detected in knockout mice compared to wild-type littermates. Apoc1 deficiency reduced the expression of ApoE mRNA (-25%, p < 0.05), but not ApoE protein levels. In line with a role for apoC-I in inflammatory processes, we observed significantly increased mRNA concentrations of the proinflammatory marker tumor necrosis factor α and oxidative stress related heme oxygenase 1 (Hmox1) in the absence of glial activation. In conclusion, the absence of ApoC-I results in impaired memory functions, which is, together with previous data, suggestive of an important, bell-shaped gene-dose dependent role for ApoC-I in appropriate brain functioning. The relative contributions of the H2 allele of APOC1 and/or APOE4 in the risk assessment in AD remain to be determined.

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Human apolipoprotein C-I expression in mice impairs learning and memory functions
Abildayeva, K., Berbée, J. F. P., Blokland, A., Jansen, P. J., Hoek, F. J., Meijer, O., Lütjohann, D., Gautier, T., Pillot, T., De Vente, J., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m700518-jlr200 · Cited by 39
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Memory Function in a Mouse Genetic Model of Alzheimer's Disease
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Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.
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Combination of Apolipoprotein E4 and High Carbohydrate Diet Reduces Hippocampal BDNF and Arc Levels and Impairs Memory in Young Mice
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Authors: Berbée, J. F. P., Vanmierlo, T., Abildayeva, K., Blokland, A., Jansen, P. J., Lütjohann, D., Gautier, T., Sijbrands, E., Prickaerts, J., Hadfoune, M., Ramaekers, F. C. S., Kuipers, F., Rensen, P. C. N., & Mulder, M.
Affiliations: Leiden University Medical Center (NL)
University of Bonn (DE)
Maastricht University (NL)
University Medical Center Groningen (NL)
Erasmus MC (NL)
Corresponding author: Mulder, Monique
ORCID: Berbée, Jimmy F.P.
Vanmierlo, Tim
Blokland, Arjan
Lütjohann, Dieter
Gautier, Thomas
Sijbrands, Eric
Prickaerts, Jos
Ramaekers, Frans C.S.
Kuipers, Folkert
Rensen, Patrick C.N.
Mulder, Monique
Venue: Journal of Alzheimer's Disease
Publisher: SAGE Publications
Published: 2011-03-21
Volume: 23
Issue: 4
Pages: 737-747
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2010-100576
OpenAlex: W2125998077
Cited by: 25
References: 79
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2019: 2 · 2016: 4 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 2
FWCI: 0.69
Type: journal article
Language: en
Open access: closed
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Leiden Repository (Leiden University) (submittedVersion)
TNO Repository (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Repository hosted by TU Delft Library (TU Delft) (submittedVersion)
Research Publications (Maastricht University) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: APOC1
MeSH terms: Analysis of Variance, Animals, Brain, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Female, Gene Expression Regulation, Male, Memory Disorders, Mice, Inbred C57BL, Motor Activity, RNA, Messenger, Stereotyped Behavior, Time Factors, Tumor Necrosis Factor-alpha, Mice, Knockout, Recognition, Psychology, Mice, Apolipoprotein C-I, Apolipoprotein E4

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Apolipoprotein CI Knock-Out Mice Display Impaired Memory Functions

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