Treatment with an Amyloid-β Antibody Ameliorates Plaque Load, Learning Deficits, and Hippocampal Long-Term Potentiation in a Mouse Model of Alzheimer's Disease
Open accessAbstract
PDAPP transgenic mice overexpress a mutant form of human amyloid precursor protein under control of the platelet-derived growth factor promoter in CNS neurons that causes early onset, familial Alzheimer's disease in humans. These mice, on a mixed genetic background, have been shown to have substantial learning impairments from early ages, as well as an age-dependent decline in learning ability that has been hypothesized to be caused by amyloid-beta (Abeta) accumulation. The goals of this study were to determine: (1) whether PDAPP mice on a pure C57BL/6 background develop more severe age-dependent learning deficits than wild-type mice; (2) if so, whether Abeta accumulation accounts for the excessive decline in learning ability; and (3) whether the learning deficits are reversible, even after significant Abeta deposition. At 4-6, 10-12, or 17-19 months of age, PDAPP and littermate wild-type mice on a C57BL/6 background were tested on a 5 week water maze protocol in which the location of the escape platform changed weekly, requiring the mice to repeatedly learn new information. PDAPP mice exhibited impaired spatial learning as early as 4 months (pre-Abeta deposition), and the performance of both wild-type and PDAPP mice declined with age. However, PDAPP mice exhibited significantly greater deterioration with age. Direct evidence for the role of Abeta accumulation in the age-related worsening in PDAPP mice was provided by the observation that systemic treatment over several weeks with the anti-Abeta antibody 10D5 reduced plaque deposition, increased plasma Abeta, improved hippocampal long-term potentiation, and improved behavioral performance in aged PDAPP mice with substantial Abeta burden.
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The dose of 10D5 mAb used in this study was previously shown to be effective in removing Aβ plaques in PDAPP AD Tg mice expressing wild type murine apoE.
“The dose of 10D5 mAb used in this study was previously shown to be effective in removing Aβ plaques in PDAPP AD Tg mice expressing wild type murine apoE [9, 10, 22].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [22]
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Cites
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Self-citation
- Authors
- Hartman, R. E., Izumi, Y., Bales, K. R., Paul, S. M., Wozniak, D. F., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Eli Lilly (United States) (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-06-29
- Volume
- 25
- Issue
- 26
- Pages
- 6213-6220
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725066
- OpenAlex
- W1965214584
- Cited by
- 147
- References
- 6
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 1 · 2014: 8 · 2013: 9 · 2012: 5
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health (NS08803, AG13956, AG11355)
- National Institute on Aging (AG11355, R01AG013956, R01AG018434, R37AG013956, AG13956, P01AG011355, AG18434)
- National Institute on Drug Abuse (DA07261, T32DA007261)
- National Institute of Neurological Disorders and Stroke (P50NS008803, NS-08803)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, anti-amyloid beta antibodies, amyloid-beta deposition, amyloid plaques, spatial learning deficits, hippocampal long-term potentiation, familial Alzheimer's disease, amyloid precursor protein, water maze, plasma amyloid-beta
- MeSH terms
- Animals, Disease Models, Animal, Hippocampus, Humans, Immunization, Learning Disabilities, Mice, Inbred C57BL, Mice, Transgenic, Platelet-Derived Growth Factor, Promoter Regions, Genetic, Amyloid beta-Protein Precursor, Long-Term Potentiation, Mice, Plaque, Amyloid
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