UK’s Sanders-Brown Researchers Discover Polyamines Prevent Collection of Alzheimer’s Disease Protein

A study by several researchers at the University of Kentucky’s Sanders-Brown Center on Aging (SBCoA) was recently highlighted in AlzForum. The study focuses on polyamines, the nitrogen-packed aliphatic molecules produced by our own cells and found in the foods we eat. They have been described by some as anti-aging generators. The study led by Daniel Lee, Ph.D., associate professor, UK Department of Neuroscience, and Maj-Linda Selenica, Ph.D., assistant professor, UK Department of Molecular & Cellular Biochemistry, found that polyamines prevent the clustering of a protein known as tau, which is a hallmark in Alzheimer’s disease.

Lee says additionally they found activation of Polyamine Stress Response (PSR) in postmortem brains of those with Alzheimer’s disease. PSR can be triggered by different stressors, including traumatic brain injury, neurological disorders, and even emotional stress. PSR promotes metabolism or inactive products of polyamines, known as acetylated polyamines. Activation of the PSR increased protein aggregation, impaired memory and worsened anxiety in mice with tau.

“The study showed that larger polyamines reduced tau aggregation, but the inactive polyamines fueled aggregation," Lee said. "The study suggests that Alzheimer’s disease may activate the PSR which may drive protein aggregation and worsen memory performance and anxiety. However, the data also suggest several potential entry points of therapeutic interventions to dampen the PSR in Alzheimer’s disease.”

Several other recent papers (Shroeder S. et al 2021; Liang Y. et al 2021) showed that polyamines, namely spermidine supplementation boost mitochondrial function, clears damaged mitochondria, and increases memory in old mice and aged flies. Spermidine is found in various foods including aged cheese, mushrooms, soy products, legumes, corn and whole grains. Spermidine is abundant in a Mediterranean diet.  A study that documented health, longevity and other diseases in people starting in 1990 found that cognition slips less in older people on a polyamine-rich (spermidine) diet and spermidine supplementation correlated with higher scores on the mini-mental state exam, a memory test for cognitive decline.

Lee says these recent studies, coupled with his team’s discoveries, indicate supplementation could be a meaningful therapeutic strategy given that spermidine is a natural product, relatively inexpensive and could boost mitochondrial function and memory later in age.

“Our studies uncovered certain mechanisms of the polyamine stress response (PSR) in Alzheimer’s disease," Lee said. "We showed how polyamines and their inactive metabolites affect hallmarks of Alzheimer’s disease pathology. This might offer new insight for polyamine supplementation or strategies in the treatment of memory decline from normal aging versus memory decline from Alzheimer’s disease.”

Some of the work on this study by Lee and Selenica was done at their previous institution before arriving at UK in 2019. However, several of their current colleagues at SBCoA contributed to the work including Erin Abner, Ph.D., assistant professor, UK Department of Epidemiology, Jerry B. Hunt Jr., Chao Ma, and Huimin Liang.

Lee says the work marks exciting progress in their collective efforts to find treatments for memory decline and ultimately a cure for Alzheimer’s disease. 

“We now understand a causal link between polyamine metabolism and Alzheimer’s disease neuropathology and how the enzymes for both synthesis and degradation of polyamines impact disease progression," he said. "The growing number of studies in polyamine biology and neurodegenerative research signifies the dynamic complexity of polyamine metabolism and its relationship the neuropathology. Certainly, more studies are needed to understand polyamine metabolism in aging and the impact on neurological disorders.”

Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R01AG054559. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.