Changes in iPSC-Astrocyte morphology reflect Alzheimer's disease patient clinical markers.

Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer's disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer's disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets.

A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy.

In our brains, different neurons make appropriate connections; however, there remain few models of such circuits. We use an open microfluidic approach to build and study neuronal circuits in ways that fit easily into existing bio-medical workflows. Dumbbell-shaped circuits are built in minutes in standard Petri dishes; the aqueous phase is confined by fluid walls - interfaces between cell-growth medium and an immiscible fluorocarbon, FC40.

Early deficits in an in vitro striatal microcircuit model carrying the Parkinson's GBA-N370S mutation.

Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro.

Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease.

The brain is spatially organized and contains unique cell types, each performing diverse functions and exhibiting differential susceptibility to neurodegeneration. This is exemplified in Parkinson's disease with the preferential loss of dopaminergic neurons of the substantia nigra pars compacta. Using a Parkinson's transgenic model, we conducted a single-cell spatial transcriptomic and dopaminergic neuron translatomic analysis of young and old mouse brains.