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Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers
ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's d...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Society for Neurochemistry
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695585/ https://www.ncbi.nlm.nih.gov/pubmed/19570031 http://dx.doi.org/10.1042/AN20090015 |
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author | Lefterov, Iliya Fitz, Nicholas F Cronican, Andrea Lefterov, Preslav Staufenbiel, Matthias Koldamova, Radosveta |
author_facet | Lefterov, Iliya Fitz, Nicholas F Cronican, Andrea Lefterov, Preslav Staufenbiel, Matthias Koldamova, Radosveta |
author_sort | Lefterov, Iliya |
collection | PubMed |
description | ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's disease) mouse models. We hypothesized that deletion of only one copy of Abca1 in APP23 (where APP is amyloid precursor protein) AD model mice will aggravate memory deficits in these mice. Using the Morris Water Maze, we demonstrate that 2-year-old Abca1 heterozygous APP23 mice (referred to as APP23/het) have impaired learning during acquisition, and impaired memory retention during the probe trial when compared with age-matched wild-type mice (referred to as APP23/wt). As in our previous studies, the levels of ApoE in APP23/het mice were decreased, but the differences in the levels of Aβ and thioflavin-S-positive plaques between both groups were insignificant. Importantly, dot blot analysis demonstrated that APP23/het mice have a significantly higher level of soluble A11-positive Aβ (amyloid β protein) oligomers compared with APP23/wt which correlated negatively with cognitive performance. To confirm this finding, we performed immunohistochemistry with the A11 antibody, which revealed a significant increase of A11-positive oligomer structures in the CA1 region of hippocampi of APP23/het. This characteristic region-specific pattern of A11 staining was age-dependent and was missing in younger APP23 mice lacking Abca1. In contrast, the levels of Aβ*56, as well as other low-molecular-mass Aβ oligomers, were unchanged among the groups. Overall, the results of the present study demonstrate that in aged APP23 mice memory deficits depend on Abca1 and are likely to be mediated by the amount of Aβ oligomers deposited in the hippocampus. |
format | Text |
id | pubmed-2695585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Society for Neurochemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-26955852009-06-23 Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers Lefterov, Iliya Fitz, Nicholas F Cronican, Andrea Lefterov, Preslav Staufenbiel, Matthias Koldamova, Radosveta ASN Neuro Research Article ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's disease) mouse models. We hypothesized that deletion of only one copy of Abca1 in APP23 (where APP is amyloid precursor protein) AD model mice will aggravate memory deficits in these mice. Using the Morris Water Maze, we demonstrate that 2-year-old Abca1 heterozygous APP23 mice (referred to as APP23/het) have impaired learning during acquisition, and impaired memory retention during the probe trial when compared with age-matched wild-type mice (referred to as APP23/wt). As in our previous studies, the levels of ApoE in APP23/het mice were decreased, but the differences in the levels of Aβ and thioflavin-S-positive plaques between both groups were insignificant. Importantly, dot blot analysis demonstrated that APP23/het mice have a significantly higher level of soluble A11-positive Aβ (amyloid β protein) oligomers compared with APP23/wt which correlated negatively with cognitive performance. To confirm this finding, we performed immunohistochemistry with the A11 antibody, which revealed a significant increase of A11-positive oligomer structures in the CA1 region of hippocampi of APP23/het. This characteristic region-specific pattern of A11 staining was age-dependent and was missing in younger APP23 mice lacking Abca1. In contrast, the levels of Aβ*56, as well as other low-molecular-mass Aβ oligomers, were unchanged among the groups. Overall, the results of the present study demonstrate that in aged APP23 mice memory deficits depend on Abca1 and are likely to be mediated by the amount of Aβ oligomers deposited in the hippocampus. American Society for Neurochemistry 2009-04-30 /pmc/articles/PMC2695585/ /pubmed/19570031 http://dx.doi.org/10.1042/AN20090015 Text en © 2009 The Author(s). http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commerical use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Lefterov, Iliya Fitz, Nicholas F Cronican, Andrea Lefterov, Preslav Staufenbiel, Matthias Koldamova, Radosveta Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title | Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title_full | Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title_fullStr | Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title_full_unstemmed | Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title_short | Memory deficits in APP23/Abca1(+/−) mice correlate with the level of Aβ oligomers |
title_sort | memory deficits in app23/abca1(+/−) mice correlate with the level of aβ oligomers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695585/ https://www.ncbi.nlm.nih.gov/pubmed/19570031 http://dx.doi.org/10.1042/AN20090015 |
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