Rudolph Tanzi, a neuroscientist at Massachusetts General Hospital and Mass General Brigham, is set to receive up to $41 million in federal funding to advance research into Alzheimer’s disease, alongside an additional $25 million from private philanthropy. The funding, announced Wednesday, will support a four-year clinical study testing multiple drug combinations developed by Tanzi and his team targeting the most common form of dementia.

At 68 years old, Tanzi remains deeply engaged in research, leading the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital, where he has worked since 1980. Over four decades, Tanzi has made significant contributions to Alzheimer’s research, including the discovery of key genes linked to both early- and late-onset forms of the disease, as well as genes associated with neuroinflammation in Alzheimer’s.

Alzheimer’s disease affects more than 7 million people in the United States and is regarded as one of the most feared neurodegenerative conditions among older adults. While several new therapies have been approved recently, including Biogen and Eisai’s leqembi in 2023, these treatments often come with high costs and potential side effects such as brain microbleeds.

Tanzi’s scientific reputation is well established, with over 800 published papers, and his work has earned recognition from peers including Dr. Sam Gandy, a professor at Mount Sinai Health System, who described Tanzi as a pioneering figure in Alzheimer’s genetics and molecular biology.

One of Tanzi’s notable accomplishments came in 2014 when his team developed an “Alzheimer’s in a dish” model—a laboratory system using human brain cells that replicate hallmark features of the disease, such as amyloid plaques and tau tangles. This breakthrough provides a faster and more reliable platform to screen potential drug candidates, overcoming limitations of previous animal models.

Using this model, Tanzi’s team screened approximately 2,000 existing drugs and 4,000 natural compounds to identify substances with potential therapeutic effects against Alzheimer’s. From this screen, five to ten combinations of drugs were selected for upcoming clinical trials funded through the Advanced Research Projects Agency for Health (ARPA-H), part of the U.S. Department of Health and Human Services.

The initial trial phase will involve 300 participants who exhibit biomarkers for Alzheimer’s, including amyloid plaques and tau protein abnormalities. Groups of 60 patients will receive different drug combinations while a control group will receive placebo, with progress monitored through blood tests measuring these biomarkers.

In parallel, Acta Pharmaceuticals, a Boston-based biotech company co-founded by Tanzi, recently secured $24 million in seed funding to launch a clinical trial of an experimental gamma-secretase modulator—a class of drugs discovered by Tanzi and the late Steven Wagner. These modulators aim to reduce harmful amyloid protein production in the brain while preserving protective forms of the protein. The trial, initiated this month, plans to enroll 72 participants.

Tanzi envisions a future where a daily medication could prevent the buildup of amyloid plaques in at-risk individuals, potentially forestalling cognitive decline in a manner similar to how statins are used to prevent cardiovascular disease.

“This is exactly like cholesterol and heart disease,” Tanzi said. “You start taking statins when you’re young to prevent heart disease later.” The ongoing research efforts offer renewed hope for more effective strategies to combat Alzheimer’s disease.