Johns Hopkins University researchers have expanded the understanding of protein misfolding in age-related cognitive decline beyond amyloid-beta and tau. Using limited proteolysis mass spectrometry (LiP-MS), they identified over 200 misfolded proteins linked to cognitive impairment in aging rats, signaling new therapeutic targets for neurodegenerative diseases such as Alzheimer’s. This discovery challenges the traditional focus solely on visible amyloid plaques and highlights a broader array of protein structural changes impacting brain function, as detailed in Science Advances.