PT  - JOURNAL ARTICLE
AU  - Adlard, Paul A.
AU  - Perreau, Victoria M.
AU  - Pop, Viorela
AU  - Cotman, Carl W.
TI  - Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease
AID  - 10.1523/JNEUROSCI.0496-05.2005
DP  - 2005 Apr 27
TA  - The Journal of Neuroscience
PG  - 4217--4221
VI  - 25
IP  - 17
4099  - http://www.jneurosci.org/content/25/17/4217.short
4100  - http://www.jneurosci.org/content/25/17/4217.full
SO  - J. Neurosci.2005 Apr 27; 25
AB  - 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.