Johns Hopkins researchers used limited proteolysis mass spectrometry to identify over 200 misfolded proteins associated with cognitive decline in aging rat brains, suggesting that neurological conditions like Alzheimer’s involve widespread protein structural changes beyond amyloid-beta and tau aggregates. These proteins with cognition-associated structural changes (CASCs) may represent novel therapeutic targets. The study, published in Science Advances, advances understanding of protein misfolding complexity in neurodegeneration.