I have spent my entire career interested in the mysteries of the brain: what it looks like, how it works and what happens when it doesn’t. Alzheimer’s disease has been the primary focus of my professional life, starting as a young researcher looking at brain scans, and leading up to now, as the head of the research program at the Alzheimer’s Association.
It’s also affected me personally. My family gradually noticed my mother-in-law’s declining memory, wandering and confusion in the late 2000s, and, in 2009, she was diagnosed with Alzheimer’s. As an expert on the illness, I was able to answer most of my children’s questions about what grandma was experiencing. But an important question that I could not answer straightforwardly was, “What can we do about this?”
There’s no way to reverse or even stop the cognitive decline of Alzheimer’s; we’re just now seeing a promising path to slow it down. Even that seemed like a reach last March when research into the much-touted drug aducanumab was halted after three simultaneous trials all showed it to be ineffective. But in October, fortune turned, with the surprise announcement that further analysis of one of the trials revealed that the drug might indeed be effective—at least at higher doses. So aducanumab is back in the game—and with it comes new hope.
Alzheimer’s and dementia science is a relatively young field. Though Alzheimer’s was first identified a century ago, for decades it remained a black box, offering no clues about the mechanics underlying its devastating symptoms. Then, 40 years ago, scientists discovered beta-amyloid, a protein which they suspected was contributing to brain cell death in Alzheimer’s. Once that potential connection was found, investigators at least had a direction for their work, and funding into researching the disease began in earnest.
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Research focused on beta-amyloid, however, hasn’t panned out in the way many had hoped. Many of the late-stage drug trials reporting negative results in recent years have been tests of treatments targeting the protein. There’s a silver lining, however: much of the knowledge we have gained about other potential treatments, and how to properly conduct clinical trials in people with and at risk for Alzheimer’s, has been from studies that, by the standard metrics, would be considered failures.
Researchers are still trying to understand the role of beta-amyloid in Alzheimer’s disease, but are also exploring new potential treatment targets ranging from brain inflammation to the gut microbiome. It’s found that bone marrow stem cells are effective at fighting inflammation—and there is now research underway into whether they could do the same if introduced into the brain. Our understanding of the role of the gut microbiome in Alzheimer’s is in its infancy, but, thanks to the early research focused on beta-amyloid, we now know that lipids and other digestive chemicals wind up in the brain, which means they might be manipulated microbially as a treatment approach.
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Early research has also led to new technologies for early diagnosis. Ten years ago, a blood test for Alzheimer’s was wishful thinking. Today, we know there are more than a dozen different kinds of blood markers for Alzheimer’s that may be detectable in the blood. Early diagnosis can mean earlier treatment—at least when effective treatments become available. Even before that, early detection can mean an early start on lifestyle changes that can slow the onset of symptoms. These are just a few elements of the vast spectrum of research underway. A few months ago, nearly 6,000 dementia researchers presented a record number of scientific studies at the Alzheimer’s Association International Conference.
Historically, an enormous challenge for research in complicated diseases like Alzheimer’s has been that promising early science can often get stuck in a sort of limbo known within the scientific community as the “valley of death”—the divide between the earliest steps in research and human clinical trials. The cause for such a divide in this case is simple: money. Potentially promising high-risk, high-yield research efforts often stall because they are too novel or too risky for the government or pharmaceutical companies to support. Non-profit and private sector funding can and must play a vital role in filling the current gap. CAR-T therapy, which uses a genetically modified T-cell receptor to help fight non-Hodgkin’s lymphoma, is an example of a treatment that actually made it out of the valley of death, thanks to non-profit/private sector funding. Treatments for Alzheimer’s could be another.
Working with San Francisco-based philanthropist Mikey Hoag, we created the Alzheimer’s Association’s Part the Cloud research grant program. In just seven years, this initiative has provided $30 million in grants to 39 state-of-the-art research projects paving new paths of discovery in everything from neuroinflammation to brain energy and metabolism. Even more importantly, our grant recipients have been able to get additional funding totaling more than $259 million from the National Institutes of Health, the National Institute on Aging, venture capital firms and other sources. All of this is a financial windfall in a research field that has been underfunded for too long.
When bold investments in research were made in other diseases—such as CAR-T or, more famously, on antiretroviral drugs for HIV infection—therapeutic doors opened and lives were saved. In August 2019, the FDA was sufficiently impressed by CAR-T’s results that it granted the procedure what is known as breakthrough therapy status, intended to speed development of drugs or treatments that show particular promise. A $9 million research grant from the California Institute for Regenerative Medicine was just one of the hit-the-gas results of the treatment’s new status. Part the Cloud is hoping to turbocharge Alzheimer’s treatments and therapies in similar ways.
We are on the verge of something truly transformational. The first survivor of Alzheimer’s disease may be reading this story now. It’s not a matter of if we will find an answer; it’s a matter of when.
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