Neocortical synaptic bouton number is maintained despite robust amyloid deposition in APP23 transgenic mice
Abstract
Major pathological findings in Alzheimer's disease (AD) brain include the deposition of amyloid-beta and synapse loss. Synaptic loss has been shown to correlate with the cognitive decline in AD patients, but the relationship between cerebral amyloidosis and synapse loss is complicated by the presence of neurofibrillary tangles and other lesions in AD brain. With the use of the APP23 transgenic mouse model that overexpresses human amyloid precursor protein (APP) with the Swedish double mutation, we investigated whether the development of cortical amyloid deposition was accompanied by synaptic bouton loss. With stereological methods, we show that despite robust age-related cortical amyloid deposition with associated synaptic degeneration, the total number of cortical synaptophysin-positive presynaptic terminals is not changed in 24-month-old animals compared with 3-, 8-, and 15-month-old APP23 mice. Wild-type mice also do not show an age-related loss of presynaptic boutons in the neocortex and are not significantly different from APP23 mice. Synaptophysin Western blotting revealed no significant difference between APP23 mice and wild-type controls at 3 and 25 months of age. Our results suggest that cerebral amyloidosis is not sufficient to account for the global synapse loss in AD. Alternatively, a putative trophic effect of APP may prevent, compensate, or delay a loss of synapses in this mouse model.
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- Authors
- Boncristiano, S., Calhoun, M. E., Howard, V., Bondolfi, L., Kaeser, S. A., Wiederhold, K.-H., Staufenbiel, M., & Jucker, M.
- Affiliations
- University of Basel (CH)
- Novartis (Switzerland) (CH)
- Corresponding author
- Jucker, Mathias
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 26
- Issue
- 5
- Pages
- 607-613
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2058813140
- Cited by
- 68
- References
- 12
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 9 · 2012: 6
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for the National Institutes of Health
- Universität Basel
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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 deposition, cerebral amyloidosis, synaptic loss, synaptophysin, presynaptic terminals, synaptic boutons, APP23 transgenic mice, amyloid precursor protein, neocortex, synapse maintenance
- MeSH terms
- Age Factors, Alzheimer Disease, Amyloid, Amyloidosis, Animals, Cell Count, Disease Models, Animal, Immunohistochemistry, Mice, Transgenic, Synapses, Blotting, Western, Amyloid beta-Protein Precursor, Synaptophysin, Presynaptic Terminals, Neocortex, Mice
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