APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy
Open accessAbstract
Abeta accumulation has an important function in the etiology of Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and changes in personality. However, the mode of this toxic activity is still a matter of scientific debate. We used the APP/PS1KI mouse model for AD, because it is the only model so far which develops 50% hippocampal CA1 neuron loss at the age of 1 year. Previously, we have shown that this model develops severe learning deficits occurring much earlier at the age of 6 months. This observation prompted us to study the anatomical and cellular basis at this time point in more detail. In the current report, we observed that at 6 months of age there is already a 33% CA1 neuron loss and an 18% atrophy of the hippocampus, together with a drastic reduction of long-term potentiation and disrupted paired pulse facilitation. Interestingly, at 4 months of age, there was no long-term potentiation deficit in CA1. This was accompanied by reduced levels of pre- and post-synaptic markers. We also observed that intraneuronal and total amount of different Abeta peptides including N-modified, fibrillar and oligomeric Abeta species increased and coincided well with CA1 neuron loss. Overall, these data provide the basis for the observed robust working memory deficits in this mouse model for AD at 6 months of age.
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In APP/PS1KI mice, a loss of ~30% of CA1 neurons was demonstrated already in 6-month-old animals, coinciding with strong intraneuronal accumulation of full-length, N-terminally truncated, pyroglutamate-modified, and oligomeric Aβ species.
“More thorough follow-up studies demonstrated a loss of ~30% of CA1 neurons already in 6-month-old animals, coinciding with a strong intraneuronal accumulation of full-length, but also N-terminally truncated, pyroglutamate-modified, as well as oligomeric Aβ species [82].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [82]
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“In the thalamus or the striatum, representing regions where only extracellular plaques are detectable, no neuron loss could be demonstrated (Breyhan et al., 2009; Casas et al., 2004; Christensen et al., 2008; Christensen et al., 2010), arguing against a Fig.”
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“More thorough follow-up studies demonstrated a loss of ~30% of CA1 neurons already in 6-month-old animals, coinciding with a strong intraneuronal accumulation of full-length, but also N-terminally truncated, pyroglutamate-modified, as well as oligomeric Aβ species [82].”
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- Authors
- Breyhan, H., Wirths, O., Duan, K., Marcello, A., Rettig, J., & Bayer, T. A.
- Affiliations
- University of Göttingen (DE)
- Saarland University (DE)
- Corresponding author
- Bayer, Thomas A.
- Venue
- Acta Neuropathologica
- Published
- 2009-04-23
- Volume
- 117
- Issue
- 6
- Pages
- 677-685
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W1979170530
- Cited by
- 87
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 5 · 2013: 10 · 2012: 6
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Acta Neuropathologica (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- Alzheimer Forschung Initiative
- European Commission (MEST-CT-2005-020013)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, hippocampal atrophy, synaptic deficits, long-term potentiation, paired-pulse facilitation, intraneuronal amyloid-beta, amyloid-beta oligomers, working memory deficits, mouse model
- MeSH terms
- Alzheimer Disease, Animals, Atrophy, Disease Models, Animal, Hippocampus, Humans, Mice, Transgenic, Neurons, Peptides, Receptors, Cell Surface, Synapses, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cell Death, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Mice, Presenilin-1, Protease Nexins, In Vitro Techniques
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