ABOVE: University of Minnesota researchers have developed genetically modified mice to study different aspects of Alzheimer's disease. Pictured are some of the neurofibrillary tangles associated with dementia.
Unforgettable discoveries
Minnesota researchers are unraveling the mysteries of Alzheimer's disease
When German physician Alois Alzheimer first reported in 1906 on the disease that now bears his name, he described two abnormal structures in the brain called plaques and tangles. This discovery was the beginning of a complicated mystery.
What are plaques and tangles made of? What do they do to the brain? Do they actually cause memory loss and dementia? Or are they just fingerprints left at the scene of a pathological crime?
These questions are challenging, especially since autopsied human brains can only reveal the disease in its final stages. Studies of living cells in a laboratory provide valuable insight into disease processes but may not reveal what actually happens in a person.
Karen Hsiao Ashe, M.D., Ph.D., and her research team recently identified the molecule known as A?* as the memory-impairing agent in mice modeling Alzheimer's disease. They also found that the rats' memory impairment was reversible, providing hope that memory loss associated with Alzheimer's may someday be corrected in humans.
A path to new discoveries
To make sense of Alzheimer's disease, the research community needed a living laboratory in which scientists could observe the disease from beginning to end. Enter the mighty mouse model — and the groundbreaking work of Karen Hsiao Ashe, M.D., Ph.D., professor of neurology and neuro-science at the University of Minnesota and holder of the Edmund Wallace and Anne Marie Tulloch Chairs in Neurology and Neuroscience.
Mice do not actually develop Alzheimer's disease, but laboratory engineering with a mutated human gene can repro-duce features of the disease in mice. In 1996 Ashe and her lab team developed the first Alzheimer's disease–like mouse in which researchers could observe both memory loss and plaques. And it was the first model made widely available, enabling scientists around the world to compare their findings.
Since then, Ashe and her team have manipulated the genetic makeup of mice to create models of different aspects of the disease. Last year, while working with a model created to develop the neurofibrillary tangles associated with demetia, they discovered that they could actually reverse memory loss. It's a breakthrough that directly contradicts the long-held belief that the effects of Alzheimer's disease are permanent. That research was published last July in the journal Science.
Recently Ashe's work has yielded an even larger discovery — an answer to one of the most puzzling questions in Alzheimer's disease research: What causes memory loss? The answer appears to be, at least in part, a tiny molecule Ashe has dubbed Aß* (or "a-beta-star"). The team published their findings in the March 16 issue of the journal Nature.
Such discoveries are urgently needed. Right now, about 4.5 million people in the United States have Alzheimer's, and this number could nearly triple by 2050. The University of Minnesota is well positioned to confront this crisis and to translate findings about disease-related molecules into medications that can stem the loss of memories and lives to a devastating illness.