The National Institutes of Health (NIH) conducts and supports a balanced and varied program of research that investigates the biological, translational, clinical, behavioral, and societal aspects of Alzheimer’s disease. This strategy has led to new insights and improved scientific tools and methods to help unravel the complexities of Alzheimer’s disease and age-related cognitive decline. Specifically, in the past few years, technological advances have enabled researchers to share, process, and analyze vast amounts of data, to look inside the living brain to identify Alzheimer’s-related changes, and to develop biological and imaging tests that detect disease onset and progression.
In 2011 and the first half of 2012, advances have been made in key areas.
Abnormal levels of amyloid and tau proteins—two hallmarks of the disease—are of intense interest to researchers. Figuring out how these proteins and other factors are involved in the disease is critical to the development of possible new treatments. Only recently have researchers found that nearly half of the brains of cognitively normal people in their 80s and 90s had Alzheimer’s-related changes, as well as signs of other neurodegenerative diseases. Why those people, with such brain changes, remained cognitively intact while others did not is still unknown. Intriguingly, in one study, researchers were able to track the spread of abnormal tau from one brain region to the next in mice, following its path of tangle formation and synapse damage. Research showing that tau disrupts mitochondria function—the cell’s energy source—is another fruitful area of investigation.
In older people with cognitive impairment, the brain may atrophy beyond the normal loss that occurs with aging. The yellow and red in this image reveal brain regions with accelerated loss of gray matter—where neurons and dendrites are found—that takes place over time in cognitively impaired older people.
Courtesy of Baltimore Longitudinal Study of Aging.
International teams of researchers are working together to identify the gene variants that play a role in Alzheimer’s disease risk and progression. For example, scientists have found that a gene called presenilin 1, which plays a role in regulating amyloid levels, may also influence synaptic plasticity, the ability of synapses to weaken or strengthen connections with other synapses. This function is important to learning and memory.
While age and genetics are the best known risk factors for dementia and cognitive decline, it is believed that a person’s life history and overall health can also influence disease risk. Scientists are finding that sleep apnea, for example, may play a role in cognitive decline.
Translational research involves a multitude of disciplines and processes to move a discovery in the laboratory into the development of a therapeutic. Researchers are targeting compounds and drugs that inhibit Alzheimer’s-related cellular changes in the brain, and an active drug discovery and preclinical research program is underway. Translational research also investigates medications already approved for other conditions that may be applied to Alzheimer’s and cognitive decline. Recently, scientists found that paclitaxel, a cancer drug, stabilized tau levels in animals. Other researchers set their sights on an existing cancer treatment that lowered amyloid levels in mice.
Researchers are looking for reliable ways to find the earliest signs of Alzheimer’s-related brain changes so that treatment and, ultimately, prevention can be targeted before clinical symptoms emerge. Investigators imaged brains and found that reduced glucose uptake, a condition associated with diabetes, and structural changes (thinning of the cerebral cortex) are markers for Alzheimer’s risk in cognitively normal older people. Imaging technology is also improving with the development of an easy-to-use but highly effective amyloid imaging agent called florbetapir.
A wide array of NIH-supported clinical trials to prevent and treat Alzheimer’s and cognitive decline are underway. New prevention trials are focusing on those at highest risk for developing the disease. Researchers are testing many possible treatments, including amyloid-clearing medications, aerobic fitness, and diabetes drugs, to see if they improve cognition in cognitively normal older people and in those with mild cognitive impairment.