How to Reverse Alzheimer’s

MIT neuroscientists have found a way to reverse neurodegeneration and other symptoms of Alzheimer’s disease by interfering with an enzyme that is typically overactive in the brains of Alzheimer’s patients. When the researchers treated mice with a peptide that blocks the hyperactive version of an enzyme called CDK5, they found dramatic reductions in neurodegeneration and DNA damage in the brain. These mice also showed improvements in their ability to perform tasks such as learning to navigate a water maze.

We found that the effect of this peptide is just remarkable,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the senior author of the study. “We saw wonderful effects in terms of reducing neurodegeneration and neuroinflammatory responses, and even rescuing behavior deficits.

With further testing, the researchers hope that the peptide could eventually be used as a treatment for patients with Alzheimer’s disease and other forms of dementia that have CDK5 overactivation. The peptide does not interfere with CDK1, an essential enzyme that is structurally similar to CDK5, and it is similar in size to other peptide drugs that are used in clinical applicationsPicower Institute Research Scientist Ping-Chieh Pao is the lead author of the paper, which appears this week in the Proceedings of the National Academy of Sciences. Tsai has been studying CDK5’s role in Alzheimer’s disease and other neurodegenerative diseases since early in her career. As a postdoc, she identified and cloned the CDK5 gene, which encodes a type of enzyme known as a cyclin-dependent kinase. Most of the other cyclin-dependent kinases are involved in controlling cell division, but CDK5 is not. Instead, it plays important roles in the development of the central nervous system, and also helps to regulate synaptic function.


Alzheimer’s: Why Certain Frequencies Blast Amyloid Plaques

In 1906, a German psychiatrist and neuroanatomist performed an autopsy on the brain of a patient who displayed abnormal symptoms while alive. Over the course of several years, this woman’s behavior, as well as her speech and language, became erratic. She forgot who people were, became paranoid, and, as her condition worsened, suffered total memory loss. When her doctor dissected her brain, he found unusual plaques and neurofibrillary tangles in her cerebral cortex. He quickly alerted his colleagues of this “peculiar severe disease.” The doctor was Alois Alzheimer. More than a century later, the medical community is still trying to understand Alzheimer’s disease (AD), a neurodegenerative brain disorder. But early studies have demonstrated that we may be able to mitigate some of the damage created by AD simply by exposing people to certain waves of sound and light.

Li-Huei Tsai, a neuroscientist and the director of the Picower Institute for Learning and Memory in the Department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology has spent the past three decades working to understand and treat neurodegenerative diseases, in particular AD.

It has not turned out to be a disease attributable to just one runaway protein or just one gene,” Li- Huei explained in a 2021 op-ed in The Boston Globe. “In fact, although Alzheimer’s is referred to as a single name, we in the Alzheimer’s research community don’t yet know how many different types of Alzheimer’s there may be, and, therefore, how many different treatments might ultimately prove necessary across the population.”

AD researchers have traditionally pursued small-molecule pharmaceuticals and immunotherapies that target a single errant protein, the amyloid. But Li-Huei believes Alzheimer’s to be a broader systemic breakdown, and she has thought about more encompassing, and hopefully effective, treatments. For several years now, her lab has pursued novel approaches using the aesthetic interventions of light and sound. We know the influence that light and sound have on the human body. People suffering from seasonal affective disorder benefit from light therapy. Blue light before bed stimulates our brain and disrupts sleep. Sound vibrations change our physiology. But how might this work on a brain experiencing AD?