Alzheimer's Disease (AD) In Vitro Modeling Service
Alzheimer's disease (AD), the most prevalent neurodegenerative disorder affecting millions worldwide, is characterized by the accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles of hyperphosphorylated tau protein, synaptic dysfunction, and chronic neuroinflammation. In vitro models of AD are indispensable for dissecting disease mechanisms, identifying therapeutic targets, and validating drug candidates.
Creative Biolabs is proud to offer a diverse range of cutting-edge in vitro models designed to accelerate your AD research and drug discovery efforts. Our models provide a controlled and reproducible environment to study the complex mechanisms underlying AD, from amyloid plaque formation and tau tangles to neuroinflammation and blood-brain barrier dysfunction.
Understanding AD: Key Mechanisms and Cellular Targets
AD pathology involves multiple cell types and interconnected processes:
- Aβ toxicity: Aggregation of Aβ peptides (Aβ40/42) into oligomers and fibrils, disrupting synaptic function and triggering neuronal apoptosis.
- Tau hyperphosphorylation: Misfolded tau proteins form neurofibrillary tangles, impairing axonal transport and destabilizing microtubules.
- Neuroinflammation: Activated microglia and astrocytes release pro-inflammatory cytokines (e.g., IL-6, TNF-α) and reactive oxygen species (ROS), exacerbating neuronal damage.
- BBB dysfunction: Impaired Aβ clearance and immune cell infiltration due to endothelial cell damage.
Key cellular targets:
- Neurons: Cortical and hippocampal neurons to study Aβ-induced synaptic loss and tau pathology.
- Astrocytes: Models for Aβ clearance (e.g., via AQP4 water channels) and inflammatory responses.
- Microglia: Phagocytic clearance of Aβ and secretion of neurotoxic factors.
- BBB components: Brain microvascular endothelial cells, pericytes, and astrocytes to study Aβ transport and neurovascular dysfunction.
Advanced Models for AD Research
Creative Biolabs offers a diverse portfolio of cutting-edge in vitro models designed to accelerate your AD research:
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iPSC-derived Models
- Patient-specific iPSCs: Generated from sporadic or familial AD patients (e.g., APOE4/4, PSEN1/2 mutations), these neurons exhibit elevated Aβ42/Aβ40 ratios and phosphorylated tau.
- Isogenic controls: CRISPR-corrected iPSC lines enable comparison of disease-specific phenotypes.
- 3D organoids: Cortical organoids with Aβ plaques and tau tangles mimic late-stage AD pathology.
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Immortalized Cell Lines
- Neuroblastoma lines (SH-SY5Y): Overexpression of APP or tau mutants (e.g., P301L) to study Aβ production or tau aggregation.
- Microglial lines (HMC3, BV-2, N9): Used to model Aβ-induced inflammation.
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Primary Rodent Cultures
- Primary cortical/hippocampal neurons: Acute Aβ42 treatment induces synaptic loss and tau phosphorylation.
- Astrocyte-neuron co-cultures: Astrocytes exacerbate or mitigate Aβ toxicity depending on activation state.
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Advanced Bioengineered Platforms
- Microfluidic BBB models: Compartmentalized systems with endothelial cells, astrocytes, and neurons to study Aβ clearance and immune cell trafficking.
- Synaptosome assays: Isolated synaptic terminals from AD model mice test Aβ oligomer binding and toxicity.
Common Assays for AD In Vitro Research
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Aβ and Tau Pathology
- Aβ ELISA: Quantifies Aβ40/42 levels in conditioned media (e.g., iPSC-derived neurons).
- Thioflavin T staining: Detects Aβ fibrils and tau tangles via fluorescence microscopy.
- Tau seeding assays: Preformed tau fibrils added to neurons induce endogenous tau aggregation.
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Synaptic Dysfunction
- Electrophysiology: Patch-clamp recordings reveal reduced mEPSC frequency in Aβ-treated neurons.
- High-content imaging: Synaptophysin and PSD-95 immunostaining quantify synaptic density.
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Neuroinflammation
- Cytokine multiplex assays: Measure IL-6, TNF-α, and IL-1β in microglial supernatants.
- ROS detection: DCFDA or MitoSOX probes quantify oxidative stress in astrocytes.
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BBB Integrity
- TEER measurements: Assess endothelial barrier function under Aβ exposure.
- Dextran permeability: Fluorescent dextran leakage indicates BBB breakdown.
Related Services
- Amyloid-beta Peptide Oligomerization Assay
- Toxic Amyloid-beta Peptide 1-42 Exposure Assay
- Amyloid-beta Induced Toxicity Assay
- Amyloid-beta Aggregates Determination Assay
- Tau Phosphorylation Assay
- Tau Hyperphosphorylation Assay
- Tau Aggregation Assay
- Tau Uptake and Seeding Assay
- Tau Clearance Assay
- APP Processing Assay
- Gamma Secretase Activity Assay
- Amyloid-beta 42 Inhibitor Screening Assay
- Tau Degradation Assay
- Aβ Induced Phagocytosis and Inflammation Assay
Let's Work Together to Conquer Alzheimer's
We are passionate about supporting researchers in their quest to understand and ultimately conquer AD. Contact us today to discuss your research needs and explore how our in vitro models and services can accelerate your drug discovery efforts. Together, we can make a difference in the fight against AD.
Reference
- Penney, J et al., "Modeling Alzheimer's disease with iPSC-derived brain cells". Mol Psychiatry 2020;25:148–167. Distributed under Open Access License CC BY 4.0 without modification.
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