The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Hippocampal Neuron Loss Exceeds Amyloid Plaque Load in a Transgenic Mouse Model of Alzheimer's Disease
Open accessAbstract
According to the "amyloid hypothesis of Alzheimer's disease," beta-amyloid is the primary driving force in Alzheimer's disease pathogenesis. Despite the development of many transgenic mouse lines developing abundant beta-amyloid-containing plaques in the brain, the actual link between amyloid plaques and neuron loss has not been clearly established, as reports on neuron loss in these models have remained controversial. We investigated transgenic mice expressing human mutant amyloid precursor protein APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L). Stereologic and image analyses revealed substantial age-related neuron loss in the hippocampal pyramidal cell layer of APP/PS-1 double-transgenic mice. The loss of neurons was observed at sites of Abeta aggregation and surrounding astrocytes but, most importantly, was also clearly observed in areas of the parenchyma distant from plaques. These findings point to the potential involvement of more than one mechanism in hippocampal neuron loss in this APP/PS-1 double-transgenic mouse model of Alzheimer's disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interestingly, the level of hippocampal pyramidal cell loss exceeded the amount explainable by the pure presence of extracellular plaque deposition by approximately 10%, indicating the involvement of more than one mechanism in hippocampal neuron loss in this mouse model [50].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [50]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Like 5XFADmice,theneuronloss in APP SL PS1KI mice is preceded by intraneuronal A 𝛃 , although intraneuronal A 𝛃 does not appear to cause amyloid plaque formation in this model.”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Schmitz et al., 2004
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, a recent APP/PS1 line coexpressing APP K670N/M671L plus V717I and PS1 M233T plus L235P (APP SL PS1KI) exhibits significant neuron death in CA1/2 of the hippocampus (Casas et al., 2004; Schmitz et al., 2004).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Schmitz et al., 2004
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In 17-month-old APP751SL/PS1M146L mice, a loss of CA1–3 neurons of ~30% compared to age-matched PS1 control animals was demonstrated by unbiased stereological counting methods.”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [50]
The cited source says what the claim attributes to it.
In the citing paper
“Some AD transgenic mice also display intraneuronal A 𝛃 (Takahashi et al., 2002; Oddo et al., 2003; Schmitz et al., 2004).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Schmitz et al., 2004
The cited source says what the claim attributes to it.
In the citing paper
“Like 5XFADmice,theneuronloss in APP SL PS1KI mice is preceded by intraneuronal A 𝛃 , although intraneuronal A 𝛃 does not appear to cause amyloid plaque formation in this model.”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Schmitz et al., 2004
In the citing paper
“PS1/APP mutant transgenic mice were shown to have prominent intraneuronal Aβ accumulation associated with neuron cell death [23, 35, 167].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [167]
In the citing paper
“Emerging data, such as FAD mutations noted above, and the direct association of intraneuronal Aβ42 with subcellular pathology [187, 188], cell death [23, 167], and behavioral and physiological abnormalities, even prior to plaques, in AD transgenic mouse models [140], are providing increasing evidence for the importance of intraneuronal Aβ.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [167]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
The efficiency of systematic sampling in stereology and its prediction*
Gundersen, H. J. G., & Jensen, E. B. V. (1987) · Journal of Microscopy · doi:10.1111/j.1365-2818.1987.tb02837.x · Cited by 3,519
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271
Adult mouse astrocytes degrade amyloid-β in vitro and in situ
Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anankov, R., Yan, F., Silverstein, S. C., & Husemann, J. (2003) · Nature Medicine · doi:10.1038/nm838 · Cited by 909
Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04183.2001 · Cited by 777
Moechars, D., Dewachter, I., Lorent, K., Reversé, D., Baekelandt, V., Naidu, A., Tesseur, I., Spittaels, K., Haute, C. V. D., Checler, F., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6483 · Cited by 668
Cited by
Sorted by citations
Items 101–108 of 108
Gray and white matter degeneration revealed by diffusion in an Alzheimer mouse model
Zerbi, V., Kleinnijenhuis, M., Fang, X., Jansen, D., Veltien, A., Van Asten, J., Timmer, N., Dederen, P. J., Kiliaan, A. J., & Heerschap, A. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.017 · Cited by 74
Antonios, G., Saiepour, N., Bouter, Y., Richard, B. C., Paetau, A., Verkkoniemi-Ahola, A., Lannfelt, L., Ingelsson, M., Kovacs, G. G., Pillot, T., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-56 · Cited by 53
Self-citationSynaptic contact number and size in stratum radiatum CA1 of APP/PS1ΔE9 transgenic mice
West, M. J., Bach, G., Søderman, A., & Jensen, J. L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.009 · Cited by 48
Insights on the Use of Transgenic Mice Models in Alzheimer’s Disease Research
Pádua, M. S., Guil-Guerrero, J. L., Prates, J. A. M., & Lopes, P. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052805 · Cited by 46
Capetillo-Zarate, E., Staufenbiel, M., Abramowski, D., Haass, C., Escher, A., Stadelmann, C., Yamaguchi, H., Wiestler, O. D., & Thal, D. R. (2006) · Brain · doi:10.1093/brain/awl176 · Cited by 45
Qin, Y.-Y., Li, M.-W., Zhang, S., Zhang, Y., Zhao, L.-Y., Lei, H., Oishi, K., & Zhu, W.-Z. (2013) · Neuroradiology · doi:10.1007/s00234-013-1195-0 · Cited by 42
Lemmens, M. A. M., Sierksma, A. S. R., Rutten, B. P. F., Dennissen, F., Steinbusch, H. W. M., Lucassen, P. J., & Schmitz, C. (2011) · Brain Structure and Function · doi:10.1007/s00429-011-0305-1 · Cited by 37
Self-citationMeißner, J. N., Bouter, Y., & Bayer, T. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142868 · Cited by 16
Self-citation
Metadata
- Authors
- Schmitz, C., Rutten, B. P. F., Pielen, A., Schäfer, S., Wirths, O., Tremp, G., Czech, C., Blanchard, V., Multhaup, G., Rezaie, P., Korr, H., Steinbusch, H. W. M., Pradier, L., & Bayer, T. A.
- Affiliations
- Maastricht University (NL)
- RWTH Aachen University (DE)
- Universitätsklinikum des Saarlandes (DE)
- Sanofi (France) (FR)
- Freie Universität Berlin (DE)
- King's College London (GB)
- European Graduate School of Neuroscience (NL)
- Corresponding author
- Schmitz, Christoph
- Rutten, Bart P.F.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 164
- Issue
- 4
- Pages
- 1495-1502
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1615337
- OpenAlex
- W1976128767
- Cited by
- 281
- References
- 32
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 16 · 2016: 10 · 2015: 16 · 2014: 21 · 2013: 12 · 2012: 17
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Fritz Thyssen Stiftung
- Deutsche Forschungsgemeinschaft (Mu901)
- Internationale Stichting Alzheimer Onderzoek
- Alzheimer Forschung Initiative
- European Commission
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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, hippocampal neuronal loss, amyloid plaques, amyloid hypothesis, presenilin 1, amyloid precursor protein, pyramidal neurons, astrocytes, age-related neurodegeneration, transgenic mouse model
- MeSH terms
- Aging, Alzheimer Disease, Animals, Disease Models, Animal, Female, Gliosis, Hippocampus, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Mice, Transgenic, Nerve Degeneration, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
