The vicious cycle of protein clumping in Alzheimer's disease and normal aging

 It has long been known that a hallmark of Alzheimer's disease, and most other neurodegenerative diseases, is the clumping together of insoluble protein aggregates in the brain. During normal disease-free aging, there is also an accumulation of insoluble proteins.

To date, approaches to treatments for Alzheimer's disease have not addressed the contribution of protein insolubility as a general phenomenon, instead focusing on one or two insoluble proteins. Buck researchers have recently completed a systematic study in worms that paints an intricate picture of the connections between insoluble proteins in neurodegenerative diseases and aging. Furthermore, the work demonstrated an intervention that could reverse the toxic effects of the aggregates by boosting mitochondrial health."Based on our discoveries, targeting insoluble proteins could provide a strategy for the prevention and treatment of a variety of age-related diseases," said Edward Anderton, PhD, a postdoctoral fellow in Gordon Lithgow's lab and co-first author of a study that appears in the May 16 issue of the journal GeroScience.

"Our study shows how maintaining healthy mitochondria can combat protein clumping linked to both aging and Alzheimer's," said Manish Chamoli, PhD, a research scientist in Gordon Lithgow's and Julie Andersen's lab, and co-first author of the study. "By boosting mitochondrial health, we can potentially slow down or reverse these harmful effects, offering new ways to treat both aging and age-related diseases."

Results support the geroscience hypothesis

The strong link between insoluble proteins promoting normal aging and diseases also builds a case for the bigger picture of how aging and age-related diseases occur. "We would argue that this work really supports the geroscience hypothesis that there is a common pathway to Alzheimer's disease and aging itself," said Buck Professor Gordon Lithgow. PhD, Vice President of Academic Affairs and the senior author of the study. "Aging is driving the disease, but the factors that put you on the track toward the disease actually occur very early."

The fact that the team found a core insoluble proteome enriched with numerous proteins that had not been considered before creates new targets for exploration, said Lithgow. "In some ways it raises the flag about whether we should be thinking about what Alzheimer's looks like in very young people," he said.

Source: ScienceDaily