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Cited by 133Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Increased soluble amyloid-β peptide and memory deficits in amyloid model mice overexpressing the low-density lipoprotein receptor-related protein

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Zerbinatti, Celina V., Wozniak, David F., Cirrito, John, Cam, Judy A., Osaka, Hiroshi, Bales, Kelly R., Zhuo, Min, Paul, Steven M. +2 more·2004·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0305803101PMC PMC327153
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Abstract

Amyloid-β peptide (Aβ) is central to the pathogenesis of Alzheimer's disease, and the low-density lipoprotein receptor-related protein (LRP) has been shown to alter Aβ metabolism in vitro . Here, we show that overexpression of a functional LRP minireceptor in the brain of PDAPP mice results in age-dependent increase of soluble brain Aβ, with no changes in Aβ plaque burden. Importantly, soluble brain Aβ was found to be primarily in the form of monomers/dimers and to be highly correlated with deficits in spatial learning and memory. These results provide in vivo evidence that LRP may contribute to memory deficits typical of Alzheimer's disease by modulating the pool of small soluble forms of Aβ.

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  • Overexpression of a functional LRP1 minireceptor resulted in a 25% reduction of brain apoE levels but an age-dependent increase of soluble Aβ in the brain of PDAPP transgenic mice.

    “overexpression of a functional LRP1 minireceptor resulted in a 25% reduction of brain apoE levels, there was an age-dependent increase of soluble Aβ in the brain of PDAPP transgenic mice”

    From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Zerbinatti et al 2004

    The Results and Discussion report an age-dependent increase in soluble brain Aβ in PDAPP mice overexpressing the LRP minireceptor. But the Discussion explicitly says apoE levels were unchanged by mLRP2 overexpression, contrary to the claimed 25% reduction. Page numbers are not available in the supplied passages. (LLM, conf=0.90)

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  • In LRP1 transgenic mice, an ~25% reduction in brain apoE levels was observed, but there was an increase in soluble and insoluble Aβ in old mice.

    “Although an ~25% reduction in brain apoE levels was observed in LRP1 transgenic mice, there was an increase in soluble and insoluble Aβ in old mice (Zerbinatti et al., 2006; Zerbinatti et al., 2004).”

    From Overexpression of Low-Density Lipoprotein Receptor in the Brain Markedly Inhibits Amyloid Deposition and Increases Extracellular Aβ Clearance (2009) · cites this paper as Zerbinatti et al., 2004

    The Results report increased soluble Aβ in old PDAPP/LRP+ mice and increased insoluble Aβ in the frontal cortex, but not the hippocampus. The Discussion says apoE levels were unchanged by LRP overexpression, contrary to the claimed ~25% reduction. Page numbers were not provided in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • LRP overexpression in APP V717F mice augmented intraneuronal Aβ accumulation, exacerbated memory deficit, and caused an increase in soluble Aβ level in the brain.

    “LRP overexpression in APP V717F mice, besides augmenting intraneuronal Ab accumulation, exacerbated the memory deficit and caused an increase in soluble Ab level in the brain.41”

    From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [41]

    Materials and Methods identifies the mice as carrying APPV717F and mLRP2 transgenes. The Results report higher soluble brain Aβ and worse water-maze performance in PDAPP/LRP+ mice than in controls, but do not establish increased intraneuronal Aβ accumulation; the reported Aβ measurements are from brain extracts. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Zerbinatti, C. V., Wozniak, D. F., Cirrito, J., Cam, J. A., Osaka, H., Bales, K. R., Zhuo, M., Paul, S. M., Holtzman, D. M., & Bu, G.
Affiliations
University of Toronto (CA)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2004-01-19
Volume
101
Issue
4
Pages
1075-1080
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0305803101
PMC
PMC327153
OpenAlex
W2007048586
Cited by
133
References
43
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 9 · 2012: 12
FWCI
7.01
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • National Institute on Aging (AG11355, P 50 AG05681, P50AG005681, P01AG011355)
  • National Institute of Neurological Disorders and Stroke (NS41872, F32NS041872)
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
amyloid-beta, soluble amyloid-beta, low density lipoprotein receptor-related protein, Alzheimer's disease, memory impairment, spatial learning, PDAPP mice, amyloid-beta metabolism, brain
MeSH terms
Animals, Brain, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Memory Disorders, Mice, Inbred C3H, Solubility, Amyloid beta-Peptides, LDL-Receptor Related Proteins, Mice

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