Review on the APP/PS1KI mouse model: intraneuronal Aβ accumulation triggers axonopathy, neuron loss and working memory impairment
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Accumulating evidence points to an important role of intraneuronal Aβ as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer’s disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Aβ instead of extracellular Aβ deposition has been introduced to be the disease‐triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Aβ42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time‐point, a dramatic, age‐dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.
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Accumulation of amyloid beta, the majority of which is amyloid beta 42, occurs prior to extracellular amyloid formation, has been implicated in the onset of early cognitive alterations, and may contribute to the pathological cascade of events that lead to neuronal dysfunction and, eventually, to Alzheimer disease.
“Accumulation of A, the majority of which is A42, occurs prior to extracellular amyloid formation, has been implicated in the onset of early cognitive alterations, and may contribute to the pathological cascade of events that lead to neuronal dysfunction and, eventually, to AD (12,13).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [13]
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Experimental — accuracy not yet measuredAβ accumulation occurs prior to extracellular amyloid formation, has been implicated in the onset of early cognitive alterations, and may contribute to the pathological cascade of events that leads to neuronal dysfunction and, eventually, to AD.
“A accumulation occurs prior to extracellular amyloid formation, has been implicated in the onset of early cognitive alterations, and may contribute to the pathological cascade of events that leads to neuronal dysfunction and, eventually, to AD (12,13).”
From Molecular Basis for Increased Risk for Late-onset Alzheimer Disease Due to the Naturally Occurring L28P Mutation in Apolipoprotein E4 (2014) · cites this paper as [13]
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- Authors
- Bayer, T. A., & Wirths, O.
- Affiliations
- University of Göttingen (DE)
- Corresponding author
- Bayer, T. A.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2008-01-03
- Volume
- 7
- Issue
- s1
- Pages
- 6-11
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2029073267
- Cited by
- 60
- References
- 9
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
- Funders
- Fritz Thyssen Stiftung
- Universität des Saarlandes
- 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, axonal degeneration, axonopathy, working memory impairment, motor impairment, thoracolumbar kyphosis, neurodegeneration, amyloid precursor protein, presenilin 1
- MeSH terms
- Animals, Axons, Central Nervous System Diseases, Disease Models, Animal, Memory Disorders, Mice, Transgenic, Neurons, Amyloid beta-Protein Precursor, Mice, Presenilin-1
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