Heidi Jacobs, PhD, a researcher working toward earlier detection of Alzheimer’s disease and, ultimately, development of new interventions, is driven by a personal understanding of the profound impact the disease can have.
“My grandmother died of late-onset Alzheimer’s,” she says. “Experiencing up close how this disease robs an individual of their memories, and ultimately of who they are as a person, motivated me to figure out how we can halt the disease.”
Today, Dr. Jacobs, a clinical neuropsychologist and a neuroscientist in the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, is well on the way to achieving this goal.
Much of her work centers on a pair of toxic proteins in the brain: beta-amyloid and tau. Currently, the earliest known stages of Alzheimer’s disease are characterized by the presence of these proteins in the cortex, the outermost layer of the brain, in individuals who are not yet showing clinical symptoms. Researchers have made tremendous strides in identifying and understanding the role of the proteins in the disease. But Dr. Jacobs and her laboratory are looking to move the detection of Alzheimer’s to an even earlier stage in its progression: to before the proteins begin to affect the brain.
“Seeing” deep in the brain
To this end, Dr. Jacobs and her lab have honed in on a small structure deep in the brain called the locus coeruleus (the name is Latin for “blue spot”). Tau begins to accumulate in the locus coeruleus in early adulthood, well before it starts to collect in other areas of the brain, so imaging the structure could provide an early window onto a person’s risk of developing Alzheimer’s — early enough, perhaps, that appropriate interventions could help stave off the most devastating effects of the disease.
The problem is — or was, when the researchers began exploring this possibility — the structure’s location. Because the locus coeruleus resides deep in the brain, visualizing the tau accumulation there was not possible with existing imaging technologies.
Undaunted, the members of the lab pioneered new methods that allowed them to image the locus coeruleus using the same basic technologies. They have now shown that not only can they visualize tau-related processes in the structure using these methods, but they can also predict cognitive decline earlier and more precisely than was previously possible.
Dr. Jacobs believes that, with further development, the methods could transform our approach to detecting and managing Alzheimer’s.
“I envision that in the future, we will image the locus coeruleus of healthy individuals during their midlife years and that this can move clinical work toward healthcare — instead of disease-care,” she says. “Including the results of these scans in the standard clinical evaluation could help clinicians provide personalized lifestyle advice or enroll individuals in prevention trials to maintain a healthy brain.”
The Importance of Staying Mentally Active
The recent work also supports the idea that continuing to learn and have new experiences as we age can help mitigate the impact of Alzheimer’s.
The work links these benefits to the behavior of neurons in the locus coeruleus when we encounter something new or expend effort on a particular task, relative to when we relax or sleep. More novelty-related activity leads to lower accumulation of tau, and this is likely to protect the brain from the negative effects of amyloid or tau.
“We have shown that individuals who are more socially active during life have less tau in their locus coeruleus at death,” Dr. Jacobs says. “We also found that individuals who remain cognitively engaged during life have a more intact locus coeruleus and remain cognitively healthy, even when beta-amyloid or tau is present. Thus, engaging in novel, stimulating activities has the potential to maintain the health of the locus coeruleus, build resilience against Alzheimer’s disease-related proteins and delay this disease.”
Philanthropic support from generous donors to Mass General and the Martinos Center will allow Dr. Jacobs and her team to continue to make great progress. The researchers’ current goals are to test novel noninvasive brain stimulation methods to optimize locus coeruleus activity and ward off the initial symptoms associated with Alzheimer’s disease.
“We are also working on novel ways to measure locus coeruleus activity remotely, at home and link this to factors that increase risk for or protect against Alzheimer’s disease later in life,” says Dr. Jacobs. “In the future, this will allow us to determine a person’s individual risk for Alzheimer’s disease and work towards personalized plans for disease prevention.”
To learn more about Mass General Neuroscience, click here, and to learn how you can help advance promising therapies for Alzheimer’s disease, contact us.
