Functional characterization of a single nucleotide polymorphism associated with Alzheimer's disease in a hiPSC-based neuron model.

Neurodegenerative diseases encompass a group of debilitating conditions resulting from progressive nerve cell death. Of these, Alzheimer's disease (AD) occurs most frequently, but is currently incurable and has limited treatment success. Late onset AD, the most common form, is highly heritable but is caused by a combination of non-genetic risk factors and many low-effect genetic variants whose disease-causing mechanisms remain unclear.

Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model.

Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal models have struggled to recapitulate tau phenomena observed . Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates.