More than 200 misfolded proteins, much more than previously known, may contribute to Alzheimer's and dementia

Good news! Amazing stuff!

"For decades, the story of Alzheimer's research has been dominated by a battle between A-beta and tau amyloids, both of which can kill neurons and impact the brain's ability to function. A new study suggests, however, that these sticky brain plaques may not be operating alone. ...

researchers have identified more than 200 types of misfolded proteins in rats that could be associated with age-related cognitive decline.

Key Takeaways

• More than 200 types of misshapen proteins in the brain could be associated with age-related cognitive decline in rats.
• Researchers believe these proteins slip past a surveillance system in the cell that specifically targets and destroys malfunctioning proteins.
• A better understanding of these protein deformities in the brain could lead to better treatments and preventative measures.

...

"Our research is showing that amyloids are just the tip of the iceberg." ..."

From the abstract:

"Cognitive decline during aging represents a major societal burden, causing both personal and economic hardship in an increasingly aging population. Many studies have found that the proteostasis network, which functions to keep proteins properly folded, is impaired with age, suggesting that there may be many proteins that incur structural alterations with age.

Here, we used limited proteolysis mass spectrometry, a structural proteomic method, to globally interrogate protein conformational changes in a rat model of cognitive aging.

Specifically, we compared soluble hippocampal proteins from aged rats with preserved cognition to those from aged rats with impaired cognition.

We identified a couple hundred proteins as having undergone cognition-associated structural changes (CASCs).

We report that CASC proteins are substantially more likely to be nonrefoldable than non-CASC proteins, meaning that they typically cannot spontaneously refold to their native conformations after being chemically denatured.

These findings suggest that noncovalent, conformational alterations may be general features in cognitive decline."

More misfolded proteins than previously known may contribute to Alzheimer's and dementia | Hub "New Johns Hopkins study of rats suggests more than 200 types of misfolded proteins could be associated with age-related cognitive decline"

Proteins with cognition-associated structural changes in a rat model of aging exhibit reduced refolding capacity (open access)

Fig. 1. Measuring protein conformational changes associated with age-associated changes in cognition with LiP-MS.