Emerging hydrogel platforms for disease modeling, diagnosis, and imaging of Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the presence of amyloid plaques, neurofibrillary tangles, neurodegeneration, cognitive decline, and dementia. The exact pathogenesis is not well understood, as appropriate pathological and therapeutically relevant disease models remain limited. Hydrogels are hydrophilic, three-dimensional (3D) polymer networks composed of synthetic or natural materials and have diverse neuroscience applications, including drug delivery, tissue engineering, and regenerative medicine. Currently, hydrogel in vitro platforms are becoming increasingly explored for AD pathogenesis, as brain extracellular matrix-mimicking biodegradable components, for delivery of growth factors for neurons and other brain cells, AD-specific peptide release, engineered multi-region brain organoids, and therapeutic drug delivery. Beyond disease modeling, hydrogels are being used to evaluate emerging AD diagnostic and therapeutic strategies, such as biomarker sensing and the integration of imaging. Recent AD diagnostic platforms have leveraged hydrogels as biomolecule-capture matrices and signal-transduction elements to detect AD-associated biomarkers via minimally invasive or implantable systems. Hydrogels have also been harnessed in magnetic resonance imaging, ultrasound, computed tomography, and positron emission tomography imaging modalities to support imageable vehicles for therapeutic delivery. Such platforms hold promise for bridging physiologically relevant neurobiological investigation with more accessible, efficient clinical tools for AD. This review highlights recent advances in hydrogel-based disease models, diagnostic tools, and imaging technologies and their potential to integrate with brain organoids, artificial intelligence, and 3D printing to enhance mechanistic and translational applications for AD.