Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease

By P. Adlard, V. Perreau, V. Pop, C. Cotman. Journal of Neuroscience, 2005

823 citations recorded by the source corpus.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there are few therapeutics that affect the underlying disease mechanism. Recent epidemiological studies, however, suggest that lifestyle changes may slow the onset/progression of AD. Here we have used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade. Five months of voluntary exercise resulted in a decrease in extracellular amyloid-β (Aβ) plaques in the frontal cortex (38%; p = 0.018), the cortex at the level of the hippocampus (53%; p = 0.0003), and the hippocampus (40%; p = 0.06). This was associated with decreased cortical Aβ1-40 (35%; p = 0.005) and Aβ1-42 (22%; p = 0.04) (ELISA). The mechanism appears to be mediated by a change in the processing of the amyloid precursor protein (APP) after short-term exercise, because 1 month of activity decreased the proteolytic fragments of APP [for α-C-terminal fragment (α-CTF), 54% and p = 0.04; for β-CTF, 35% and p = 0.03]. This effect was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, may involve neuronal metabolism changes that are known to affect APP processing and to be regulated by exercise. Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant (p < 0.02) reductions in escape latencies over the first 3 (of 6) trial days. In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.

Subfields: Developmental Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/8cbdd1d4270b0b8d58bf3079ef3b19114469bde9

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Citations in the corpus

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults (2016, background): “Mouse models have also proposed that exercise reduces the load of amyloid-beta (Aβ) plaques in the hippocampus and cortex, possibly bymodulating processing of the amyloid precursor protein and by enhanced degradation and clearance of Aβ (Adlard et al., 2005).”
Exercise and the brain: something to chew on (2009, background): “In addition, running reduced the load of βamyloid plaques in both hippocampus and cortex [39].”
Calcium and neurodegeneration (2007, background): “In other studies, it was shown that voluntary exercise decreases Aβ accumulation in a mouse model of AD (Adlard et al., 2005).”
Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits (2018, background): “…converging evidence is showing that motor activity should be performed before the development of neurodegeneration in order to exert its protective role (Richter et al., 2008; Lin et al., 2015) such as before the formation of beta amyloid plaques in Alzheimer’s disease (Adlard et al., 2005).”
Enriched environments, experience-dependent plasticity and disorders of the nervous system (2006, positive): “Although this study used a small number of animals and the cognitive improvement was mild, there is additional evidence that increased exercise can lead to enhanced cognitive functio”
Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. (2008, positive): “We utilized the MWM to assess the effects of drug on spatial learning and memory, as previously described ( Adlard et al., 2005 ).”
Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence (2008, background): “Beneficial effects of exercise on reducing amyloid b plaques in the frontel cortex have been demonstrated recently in a transgenic mouse model (Adlard et al. 2005 ; Lazarov et al. 2005), which might be mediated through insulin control (Farris et al.”
Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain (2019, result): “, 2007b; Verburgh, 2015), and animal studies are consistent with this idea (Adlard et al., 2005). In particular, the risk of developing AD is highly increased in a lonely person (Wilson et al., 2007a), indicating that social interaction could delay the onset of the disease. Physical activity is anot”
Be smart, exercise your heart: exercise effects on brain and cognition (2008, background): “Aerobic activity might be neuroprotective, preventing the development of certain cognitive and neural symptoms that are associated with these diseases, through the regulation of BDNF secretio”