Cognitive and Physical Activity Differently Modulate Disease Progression in the Amyloid Precursor Protein (APP)-23 Model of Alzheimer’s Disease
Abstract
Background In aging mice, activity maintains hippocampal plasticity and adult hippocampal neurogenesis at a level corresponding to a younger age. Here we studied whether physical exercise and environmental enrichment would also affect brain plasticity in a mouse model of Alzheimer's disease (AD). Methods Amyloid precursor protein (APP)-23 mice were housed under standard or enriched conditions or in cages equipped with a running wheel. We assessed beta-amyloid plaque load, adult hippocampal neurogenesis, spatial learning, and mRNA levels of trophic factors in the brain. Results Despite stable beta-amyloid plaque load, enriched-living mice showed improved water maze performance, an up-regulation of hippocampal neurotrophin (NT-3) and brain-derived neurotrophic factor (BDNF) and increased hippocampal neurogenesis. In contrast, despite increased bodily fitness, wheel-running APP23 mice showed no change in spatial learning and no change in adult hippocampal neurogenesis but a down-regulation of hippocampal and cortical growth factors. Conclusions We conclude that structural and molecular prerequisites for activity-dependent plasticity are preserved in mutant mice with an AD-like pathology. Our study might help explain benefits of activity for the aging brain but also demonstrates differences between physical and more cognitive activity. It also suggests a possible cellular correlate for the dissociation between structural and functional pathology often found in AD.
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The extant literature provides some clues about molecular and cellular pathways supporting interactive effects of different factors, but much remains to be discovered.
“although the extant literature provides some clues concerning the molecular and cellular pathways that support the interactive effects of different factors, much remains to be discovered in further research on multimodal interventions”
From Enrichment Effects on Adult Cognitive Development: Can the Functional Capacity of Older Adults Be Preserved and Enhanced? (2008) · cites this paper as Wolf et al., 2006
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- Authors
- Wolf, S. A., Kronenberg, G., Lehmann, K., Blankenship, A., Overall, R., Staufenbiel, M., & Kempermann, G.
- Affiliations
- Max Delbrück Center (DE)
- Novartis (Switzerland) (CH)
- Corresponding author
- Kempermann, Gerd
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 60
- Issue
- 12
- Pages
- 1314-1323
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2020895118
- Cited by
- 288
- References
- 93
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 11 · 2020: 14 · 2019: 13 · 2018: 19 · 2017: 19 · 2016: 14 · 2015: 15 · 2014: 9 · 2013: 22 · 2012: 17
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, APP23 mice, physical activity, wheel running, environmental enrichment, adult hippocampal neurogenesis, hippocampal plasticity, amyloid plaques, spatial learning, brain-derived neurotrophic factor, neurotrophin-3, growth factors, cognitive activity, brain aging
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cell Count, Cerebral Cortex, Cognition, Environment, Female, Hippocampus, Insulin-Like Growth Factor I, Mice, Transgenic, Motor Activity, RNA, Messenger, Fibroblast Growth Factor 2, Amyloid beta-Protein Precursor, Disease Progression, Maze Learning, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, Nerve Growth Factor, Neurotrophin 3, Vascular Endothelial Growth Factor A, Mice
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