Neurodegeneration Organoid Modeling Service

The study of neurodegenerative diseases—including Alzheimer's, Parkinson's, and ALS—has long been hampered by a lack of preclinical models that can faithfully recapitulate the complex, progressive pathology seen in human patients. While traditional animal models have provided foundational insights, inherent species-specific differences often limit their translational predictability. Likewise, conventional 2D cell cultures fail to model the intricate three-dimensional cytoarchitecture, complex cell-cell interactions, and the slow-developing disease phenotypes that are the hallmarks of neurodegeneration.

To bridge this critical translational gap, Creative Biolabs offers a highly advanced Neurodegeneration Organoid Modeling Service. By leveraging patient-derived or genetically engineered induced pluripotent stem cells (iPSCs), we generate sophisticated 3D brain organoids that develop the complex cellular diversity and functional deficits of specific neurodegenerative disorders. These models provide an unprecedented window into human disease mechanisms, enabling the discovery and validation of next-generation therapeutics.

Disease-Specific Platforms: From Regional Pathology to Circuit Dysfunction

We offer a sophisticated portfolio of organoid models, selecting the precise anatomical system required to investigate your disease of interest with the highest fidelity.

1. Alzheimer's Disease (AD) Models

AD pathology is centered in the cortex and hippocampus. We model this using:

• Region-Specific Models: Cortical Organoids that develop complex, layered structures and neuronal populations susceptible to AD pathology. These are ideal for studying the cell-autonomous drivers of amyloid and Tau proteinopathy.
• Advanced Assembloid Models: We fuse Cortical and Hippocampal Organoids to model the entorhinal-hippocampal circuit, which is critical for memory and among the first to be affected in AD. To investigate neuroinflammation and vascular contributions, we generate vascularized neuro-immune organoids by incorporating microglia and endothelial cells.
• Key Pathological Readouts: Amyloid-β (Aβ) aggregation, Tau hyperphosphorylation, synaptic dysfunction and loss, and astrocyte- or microglia-mediated neuroinflammation.

Fig.1 Researchers generated cerebral organoids from human iPSCs to study AD.¹

2. Parkinson's Disease (PD) Models

Characterized by the loss of dopaminergic neurons in the midbrain, we investigate PD with:

• Region-Specific Models: Midbrain-Specific Organoids, which are expertly patterned to generate a high yield of functional, dopamine-producing neurons—the primary cell type lost in PD.
• Advanced Assembloid Models: We construct Midbrain-Striatal Assembloids to model the nigrostriatal pathway, allowing for the analysis of axonal connectivity, synaptic integration, and circuit-level dysfunction between these two critical regions.
• Key Pathological Readouts: α-synuclein aggregation (Lewy body-like inclusions), progressive dopaminergic neuron death, mitochondrial dysfunction, and oxidative stress.

3. Huntington's Disease (HD) Models

This disorder primarily affects the striatum and its connection with the cortex. Our models include:

• Region-Specific Models: Striatal Organoids that form matrix-like compartments and are used to study the cell-intrinsic effects of the mutant Huntingtin (mHTT) protein.
• Advanced Assembloid Models: Cortico-Striatal Assembloids are generated by fusing cortical and striatal organoids. This powerful system models the unidirectional cortico-striatal projections and allows for the study of the hyperactivity and network deficits characteristic of HD.
• Key Pathological Readouts: Formation of mHTT aggregates, neuronal circuit defects, and specific neurodegeneration within striatal compartments.

4. Amyotrophic Lateral Sclerosis (ALS) Models

To capture the degeneration of the motor system, we employ a multi-component approach:

• Region-Specific Models: Cortical Organoids to model upper motor neuron pathology and Spinal Cord Organoids to model lower motor neuron vulnerability.
• Advanced Assembloid Models: We engineer functional Cortico-Motor Assembloids by fusing cortical and spinal cord organoids, and can further integrate skeletal muscle spheroids to model the entire neuromuscular junction (NMJ) and its functional output. Co-culture with astrocytes and microglia is used to model the intense neuroinflammation that drives ALS progression.
• Key Pathological Readouts: TDP-43 proteinopathy, motor neuron death, astrocyte proliferation, and functional deficits at the NMJ.

Core Platform Technologies

• Human-Derived and Gene-Edited: We start with iPSCs from patients or use CRISPR-Cas9 to introduce specific disease-causing mutations into healthy cell lines, creating precise, isogenic models.
• Functional Circuitry with Assembloids: We are experts in the controlled fusion of multiple, distinct organoids to build assembloids, enabling the study of complex, long-range cell-cell interactions and neural circuits that are absent in single-organoid cultures.
• Integrated Neuro-Immune & Vascular Systems: We recapitulate the TME by incorporating functional microglia, astrocytes, and endothelial cells, allowing for robust studies of neuroinflammation and blood-brain barrier interactions.

Our Workflow

Model the Disease with Unprecedented Precision. Discover with Unrivaled Confidence.

Move beyond the limitations of conventional models. Partner with Creative Biolabs to leverage anatomically precise organoids and assembloids for your neurodegeneration research.

Reference

1. Zhao, J., Fu, Y., Yamazaki, Y. et al. APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids. Nat Commun 11, 5540 (2020). https://doi.org/10.1038/s41467-020-19264-0. Distributed under Open Access License CC BY 4.0. The original image was modified.