Overview

• Johns Hopkins researchers compared hippocampal proteomes of 17 two-year-old rats and identified over 200 proteins that misfold exclusively in cognitively impaired subjects.
• The misfolded proteins evade cellular quality-control systems despite not forming classical amyloid aggregates.
• Analysis covered more than 2,500 protein types, distinguishing general age-related misfolding from impairment-specific structural changes.
• Results challenge the longstanding amyloid-centric view of Alzheimer’s by revealing a broader network of proteopathies beyond amyloid-β and tau.
• The team plans high-resolution microscopy to characterize these proteins’ molecular deformities and assess their diagnostic and therapeutic potential.