When Reisa Sperling, MD, MMSc, was a neurology resident, she joined Dennis Selkoe, MD, on a clinic visit that would leave an indelible impression. At the time, Sperling — who would go on to become a luminary in the field of Alzheimer’s disease (AD) clinical research — was still deciding what area of focus she would choose for her career. That day, Sperling and Selkoe visited with a former businessman who was an Alzheimer’s patient at the hospital. He would eventually pass away from the disease. Sperling followed his case closely and still has a slide that shows the damage that the disease had wrought to his brain.
“Dennis inspired me — he was a basic scientist, and yet he was taking excellent care of patients,” Sperling recalled decades later. That patient’s story and her shared experience with Selkoe have stayed with her and moved her to have a quote written on her office wall: Remember the Reason You Do the Research.
For Sperling, Alzheimer’s research is personal, and not just because of a family history of the disease. Both Selkoe and Sperling are galvanized by the patients they see. Sperling leads large-scale clinical trials in people at risk for developing symptoms of AD, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study (A4), and conducts clinical imaging research focused on the early diagnosis and treatment of AD. In contrast, Selkoe and his lab are interested in the biochemical, molecular and cell biology that underpin the disease. While each approaches AD from a different place, they share a commitment to not just treating Alzheimer’s disease but preventing its occurrence in the first place.
That shared commitment caught the attention of Andrew and Kate Davis and the Shelby Cullom Davis Charitable Fund, which recently announced a $25 million gift to establish The Davis Alzheimer Prevention Program at the Brigham. This significant investment will be used to accelerate Sperling and Selkoe’s work to predict and ultimately prevent Alzheimer’s disease.
Understanding Alzheimer’s from A to Z
By the time Sperling met him in the early 1990s, Selkoe had already established himself as a preeminent researcher in the field. In 1978, Selkoe founded a laboratory dedicated to the study of neurodegeneration. In 1982, Selkoe and colleagues described the unusual properties of a hallmark of AD: neurofibrillary tangles. His lab was the first to make antibodies to the tangles and that led shortly to their identifying the brain protein called tau as the key constituent of the tangles. Because Selkoe suspected that the tangles of tau might occur later in the AD process, he turned his attention to the other hallmark lesion, the amyloid plaques. His lab conducted extensive experiments on the amyloid B-protein and amyloid-beta precursor protein (APP), which led Selkoe to formulate the amyloid hypothesis detailing a cascade of molecular events that lead to AD.
These advancements have set the stage for the Davis Alzheimer Prevention Program.
“The Davis gift will allow us to pursue basic research in the laboratory to find new compounds and antibodies that we can bring forward for treatment and prevention and to also pursue the idea of a set of blood tests for predicting Alzheimer’s,” said Selkoe. “There is a lot of work to be done, and this gift will dramatically enable us to accelerate and hone our efforts.”
Better Testing for Better Trials
Among the investigators’ many pursuits is the search for one or more plasma tests for AD that can detect risk of disease before the onset of symptoms. One reason for the focus on relatively simple, inexpensive blood tests is that they would help accelerate identifying individuals for large-scale prevention trials. Sperling has led the A4 Study, a prevention trial that began in 2013. Now, she is looking for ways to conduct even larger trials and get results much faster.
“Finding the right people and measuring meaningful change are two of the key elements for success in our prevention trials,” said Sperling.
In addition to novel blood tests being validated in the Selkoe lab, Sperling’s Brigham colleagues, including Rebecca Amariglio, PhD, and Kathryn Papp, PhD, are developing sophisticated cognitive tests on smart phones that can pick up clues about AD risk and progression more quickly.
“One of the things we’d like to do is ‘fail faster’ — if we don’t have the right intervention, we need to know on as short a timeframe as possible,” said Sperling.
Meeting in the Middle
One of the most exciting aspects of the Davis APP program for both Sperling and Selkoe is the opportunity to bring basic laboratory research and clinical research together — and to bring colleagues and early-investigators from both worlds into one program.
“While Dennis is working at the molecular level and I’m working at the human level, it turns out we’re often asking the same questions,” said Sperling. “We’re coming at the same goal from different sides, and meeting in the middle to tackle the same problems.”
“It’s a tremendous pleasure and privilege to have the Davis Foundation endorse what Reisa and I have done in separate venues at the Brigham and will now be brought together under one roof,” said Selkoe. “Thanks to their visionary philanthropy, we have a groundbreaking opportunity here…and real forward momentum.”