Researchers at Johns Hopkins University have used limited proteolysis mass spectrometry (LiP-MS) to uncover over 200 misfolded proteins potentially linked to age-related cognitive decline in a rat model, expanding the focus beyond amyloid-beta and tau amyloids. Published in Science Advances, their work highlights proteins with cognition-associated structural changes (CASCs) that may serve as novel therapeutic targets for Alzheimer’s and other dementias affecting the elderly. This discovery points to a more complex landscape of protein misfolding contributing to neurodegenerative diseases than previously recognized.