Improving Cell Health Could Slow Down Alzheimer’s: Study

In Alzheimer’s disease, the beta-amyloid protein forms aggregates called plaques, and these are tightly associated with areas of neuronal death and brain inflammation causing disease. However, these plaques contain hundreds of additional proteins which have been largely ignored until now. For this reason, researchers from The Buck Institute for Research on Aging in California decided to examine how the accumulation of insoluble proteins, in general, might accelerate Alzheimer’s disease. Researchers then used a compound to boost the quality of mitochondrial health in the proteins that had become insoluble, effectively delaying the toxic effects of beta-amyloid. Mitochondria, the so-called powerhouses of the cell, have recently become a focus point in Alzheimer’s research, as scientists have been trying to see whether “repairing” mitochondria that stop functioning well with age might help preserve brain health. 

According to Manish Chamoli, PhD, research scientist at The Buck Institute for Research on Aging in California and co-first author of this study, proteins are like tiny machines in cells that need to be a specific shape to work correctly. Human cells have evolved ways to either refold the proteins into the correct shape or degrade them when they’re too damaged to be refolded. In conditions such as Alzheimer’s disease, however, the brain does not correctly dispose of such proteins. 

In laboratory organisms, such as the microscopic worm Caenorhabditis elegans, labs around the world have observed that, as these worms age, they accumulate clumps of insoluble proteins. Likewise, it’s well established that Alzheimer’s disease patients’ brains accumulate protein aggregates. According to researchers, the insoluble proteins found in the core insoluble proteome have already been linked to other neurodegenerative conditions including Parkinson’s disease and Huntington’s disease. Data suggest there may be a causal role for the insoluble proteome in Alzheimer’s disease pathogenesis. For example, insoluble protein extracts from old but not young animals accelerate the aggregation of beta-amyloid. 

Next, researchers wanted to find a way to potentially reverse how beta-amyloid helps drive the insolubility of proteins. As many mitochondrial proteins become insoluble during natural ageing and beta-amyloid influence, they hypothesized that boosting mitochondrial protein quality might reverse some of beta-amyloid’s negative effects. It would be interesting to conduct clinical trials to test the efficacy of mitochondrial health-boosting compounds in Alzheimer’s disease patients, including compounds like urolithin A and other mitochondrial enhancers.