Johns Hopkins University researchers have identified over 200 misfolded proteins potentially associated with age-related cognitive decline in rats, suggesting amyloid-beta and tau proteins are not the sole contributors to Alzheimer’s and dementia. Utilizing limited proteolysis mass spectrometry (LiP-MS), the team detected subtle structural changes in proteins not forming typical amyloid clumps but still impacting brain function. These findings, published in Science Advances, may open new therapeutic targets for neurodegeneration beyond traditional amyloid-focused strategies.