Neuronal Death and Biomolecular Condensates: Are There Any New Treatment Options for Alzheimer's Disease?

Alzheimer's disease (AD) is marked by the pathological aggregation of amyloid β (Aβ) and tau proteins. Emerging research reveals that these proteins undergo liquid-liquid phase separation (LLPS), forming biomolecular condensates that promote aggregation and neurotoxicity. These phase-separated structures reshape the intracellular environment, facilitating protein misfolding and spreading. This review highlights recent advances in understanding the role of condensates in AD pathogenesis and explores novel therapeutic strategies targeting condensate dynamics. Promising approaches include small molecules that disrupt LLPS, epigenetic drugs influencing nuclear condensates, and compounds like DDL 920 and RI AG03 that modulate tau phase separation and neuroinflammation, respectively. Additionally, anti-inflammatory agents, such as nucleotide reverse transcriptase inhibitors (NRTIs), offer potential for upstream intervention. Targeting biomolecular condensates presents a next-generation strategy for AD treatment. Future research should focus on in vivo profiling of condensate composition, biomarker development, and the development of patient-specific therapies to enable early, disease-modifying interventions.