Until recently, the only treatment for Alzheimer's disease was a series of drugs that slowed but did not stop the disease's progression. But now two UW-Madison scientists have discovered that a critical protein may prevent the disease from advancing.
The protein transthyretin, appears to protect brain cells from harmful proteins linked to Alzheimer's disease, said Jeff Johnson, associate professor of pharmacy.
\Transthyretin is present in the brain in low levels, but if we can elevate those levels, it can have a therapeutic effect on brain cells,"" he said.
Alzheimer's disease, an age-related form of dementia, afflicts 4.5 million Americans and causes memory loss and personality changes. Scientists believe the disease has both genetic and environmental causes, though they are not sure how it works. Many researchers believe Alzheimer's disease is related to protein deposits that stick to patients' brain cells, causing cell death and ultimately brain shrinkage.
The deposits seem to come from the breakdown of a brain protein called amyloid precursor protein. APP can be cut in different ways, yielding what Thor Stein, a third-year UW-Madison medical student, calls ""good cuts"" and ""bad cuts."" Stein is the lead author of the report that appears in the Sept. 1 issue of the Journal of Neuroscience.
""When APP is processed to form a bad cut, the bad cut can form deposits and be toxic to brain cells. But APP can be processed a different way to make a good cut that protects brain cells from the bad cut,"" Stein said. In an ordinary brain, good cuts substantially outnumber bad cuts, but in Alzheimer's patients, this ratio is mysteriously reversed. Researchers do not know why bad cuts even exist, but still, Stein said the harmful effects of bad cuts could be mitigated by transthyretin, whose production is increased by the good cut.
""Bad cuts ultimately kill brain cells, but somehow transthyretin interferes with that process,"" Stein said.
The next step is to see if biotech companies can develop a therapy to increase transthyretin levels, though Stein cautioned an actual treatment is still years away.
Regina Murphy, professor of chemical and biological engineering, said the mechanism of Alzheimer's disease remains poorly understood.
""The deposits only tend to collect in certain parts of the brain, for some reason the parts of the brain that control memory and learning,"" she said. ""We don't know why they hit those parts, and leave other parts of the brain completely unaffected.""
