Alzheimer’s disease is a devastating neurological disease that affects an estimated 5 million people today. According to WHO, without a cure that number will balloon to an estimated 15 million by 2050.
New research has demonstrated the Alzheimer’s disease processes begins as early as 20 years before clinical symptoms appear, an asymptomatic period referred to as the “silent phase” of Alzheimer’s. This period occurs long before someone is diagnosed with Mild Cognitive Impairment (MCI) or Alzheimer’s.
Many believe that a better understanding of the proteins in the brain present during this silent phase could allow for improved pharmaceutical interventions during the early period and a better chance of success in preventing the onset of disease.
To such an end, researchers at the University of Minnesota N. Bud Grossman Center for Memory Research and Care are working to understand the role of different proteins present in the brain at different stages of Alzheimer’s disease, especially this silent phase.
World-renowned Alzheimer’s researcher Karen Hsiao Ashe, M.D., Ph.D., has developed a mouse model that mimics the early stages of Alzheimer’s disease. In this mouse model, scientists in Ashe’s laboratory discovered a specific protein, Abeta*56 which, as it turns out, appears in the brain of mice just as they become cognitively impaired.
The Abeta*56 molecule also impairs memory when injected into the brains of normal, healthy rats. These findings led Ashe to believe that Abeta*56 may be a key player in the early Alzheimer’s disease process.
Although promising, more evidence that Abeta*56 might be involved in early stage Alzheimer’s disease was needed to generate a stronger link. The problem was, the protein had only been examined in animal models. Investigation into the role of Abeta*56 in human patients suffering from Alzheimer’s disease was needed.
Under the tutelage of Ashe, University of Minnesota researcher Maureen Handoko, Ph.D., in her neuroscience graduate thesis, took the first steps to address this question. She began by measuring the levels of Abeta*56 in the spinal fluid of living human subjects. Handoko and colleagues found that the levels of Abeta*56 were elevated in people at higher risk of developing Alzheimer’s disease, which include elderly people and people with positive biomarkers predictive of Alzheimer’s disease development.
In addition, Handoko and Ashe found that, in cognitively intact elderly people, high levels of Abeta*56 were associated with elevated levels of tau, a protein that is thought to be involved in neuronal injury and degeneration in Alzheimer’s disease
“These are exciting findings, because not only did we find that Abeta*56 exists in humans, but the data also suggests that Abeta*56 may be involved in the disease process in very early stages of Alzheimer’s disease,” said Handoko.
Knowing the key molecular players in the disease process may help inform which molecules to target for therapy, offer hope for tests for early disease detection, and enhance success of future treatments of Alzheimer’s disease.
“However, more research needs to be done so we can better define the role of Abeta*56 in Alzheimer’s disease and the exact mechanism by which it contributes to memory impairment,” Handoko concluded.