Sci. Aging Knowl. Environ., 16 March 2005
Vol. 2005, Issue 11, p. nf21
[DOI: 10.1126/sageke.2005.11.nf21]


Outrunning Alzheimer's Disease

Exercise curbs {beta} amyloid buildup in mice

Mitch Leslie

A mile or two a day might keep plaques at bay, if the results of a new rodent study hold true for humans. The research reveals that mice that got off their furry little duffs amassed fewer of the brain-clogging globs seen in Alzheimer's disease (AD) patients. Activity apparently rouses an enzyme that destroys the plaque protein and spurs other salutary molecular changes in the brain.

A stack of studies suggests that older folks who work out their bodies and minds are less likely to develop AD (see "Detangling Alzheimer's Disease"). But whether activity hinders the {beta}-amyloid plaques that characterize AD remains uncertain. Researchers have tackled the question by providing rodents with an "enriched environment"--tunnels to scurry through, wheels to run in, and other toys to encourage movement--that can sharpen animals' memory, previous studies have shown. A study published last year suggested that these surroundings improved learning and memory and stabilized plaques in older mice genetically engineered to amass {beta} amyloid. A 2003 study, however, detected more {beta}-amyloid buildup in engineered mice reared in an enriched environment. Molecular neurobiologist Sangram Sisodia of the University of Chicago, Illinois, and colleagues wanted to pin down the impact of enriched environments on {beta}-amyloid accumulation.

One group of rodents spent time in the mouse gym. The other group didn't even get a miniature Bowflex. After 5 months, rodents that visited the "play" cages carried fewer, smaller {beta}-amyloid clots than did the other animals. Moreover, within the active group, the animals that spent the most time in the running wheels sported the fewest {beta}-amyloid clumps.

Enzymes make {beta} amyloid by clipping a protein called APP. The team found that the amount of APP didn't differ between the two mouse groups, but the sedentary ones showed more than twice as much free-floating {beta} amyloid in their brains. The activity of neprilysin, an enzyme that destroys {beta} amyloid, was more than 50% higher in the enriched-environment group than in the sluggards. That result suggests that exercise might fight {beta}-amyloid clumping by spurring neprilysin to demolish the protein. The researchers also detected payoffs when they used microarrays to gauge gene activity in the animals' brains. Genes that spur cell division and blood vessel growth and that buffer stress cranked up. The work adds more weight to the old saw, "What's good for the body is good for the brain," says Sisodia.

"The study is the first to show that exercise can reduce amyloid deposition," says behavioral neuroscientist Karyn Frick of Yale University. The discovery that physical activity stimulates neprilysin is compelling, says neuroscientist Mark Mattson of the National Institute on Aging in Baltimore, Maryland: "The most important finding is that this enzyme can be altered by behavior." Both researchers agree that it's crucial to determine whether the mice also remain mentally sharp. Further work might reveal whether humans can run down AD.

March 16, 2005
  1. O. Lazarov et al., Environmental enrichment reduces A{beta} levels and amyloid deposition in transgenic mice. Cell 120, 701-713 (2005). doi:10.1016/j.cell.2005.01.015 [CrossRef][Medline]
Citation: M. Leslie, Outrunning Alzheimer's Disease. Sci. Aging Knowl. Environ. 2005 (11), nf21 (2005).

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