Models

This index catalogs animal models and experimental model systems used in neurodegenerative disease research. These models are essential for understanding disease mechanisms, testing therapeutic interventions, and translating findings from basic science to clinical applications.

Model systems span multiple species from invertebrates (C. elegans, Drosophila) to mammals (mice, rats, non-human primates), each offering distinct advantages for studying specific aspects of neurodegeneration.

Alzheimer's Disease Models

5xFAD Transgenic Mouse Model

The 5xFAD model expresses five familial AD mutations (3 APP + 2 PSEN1), producing aggressive amyloid-beta pathology from 2 months of age.

This index catalogs animal models and experimental model systems used in neurodegenerative disease research. These models are essential for understanding disease mechanisms, testing therapeutic interventions, and translating findings from basic science to clinical applications.

Model systems span multiple species from invertebrates (C. elegans, Drosophila) to mammals (mice, rats, non-human primates), each offering distinct advantages for studying specific aspects of neurodegeneration.

Alzheimer's Disease Models

5xFAD Transgenic Mouse Model

The 5xFAD model expresses five familial AD mutations (3 APP + 2 PSEN1), producing aggressive amyloid-beta pathology from 2 months of age.

• [5xFAD Transgenic Mouse Model](/models/5xfad-transgenic-mouse-model)
• Mechanism: 5 mutations drive rapid Aβ42 production and aggregation
• Applications: Anti-amyloid therapy testing, amyloid cascade studies

APP/PS1 Dual Transgenic Model

The APP/PS1 model expresses mutant APP (Swedish) and PSEN1 (M146L), producing amyloid plaques from 6 months.

• [APP/PS1 Dual Transgenic Model](/models/app-ps1-dual-transgenic-model)
• Mechanism: Increased Aβ production, shifted to Aβ42 species
• Applications: Immunotherapy testing, biomarker validation

Cerebral Organoid Model

Cerebral organoids are 3D brain tissue cultures derived from stem cells, providing human models for AD and PD.

• [Cerebral Organoid Model](/models/cerebral-organoid-model)
• Mechanism: Self-organizing brain tissue recapitulates development
• Applications: Disease modeling, drug testing, mechanism studies

Parkinson's Disease Models

6-OHDA Rat Model

The 6-hydroxydopamine (6-OHDA) rat model replicates selective dopaminergic degeneration via oxidative stress.

• [6-OHDA Rat Model of Parkinson's Disease](/models/6-ohda-rat-model-parkinsons)
• Mechanism: 6-OHDA uptake via dopamine transporters causes oxidative stress
• Applications: Testing dopaminergic medications, cell transplantation

MPTP Mouse Model

MPTP is a neurotoxin that selectively destroys dopaminergic neurons via mitochondrial complex I inhibition.

• [MPTP Mouse Model of Parkinson's Disease](/models/mptp-mouse-model-parkinsons)
• Mechanism: MPTP metabolized to MPP+, inhibits complex I
• Applications: Neuroprotection, mitochondrial dysfunction studies

Alpha-Synuclein Transgenic Models

Transgenic models expressing mutant alpha-synuclein (A53T, A30P) recapitulate Lewy body formation.

• [A53T Alpha-Synuclein Transgenic Mouse Model](/models/a53t-alpha-synuclein-mouse-parkinsons)
• Mechanism: Mutant α-synuclein promotes aggregation
• Applications: Anti-aggregation therapies, Lewy body studies
• [A30P Alpha-Synuclein Transgenic Mouse Model](/models/a30p-alpha-synuclein-mouse-model)
• Mechanism: A30P mutation accelerates aggregation
• Applications: Aggregation mechanism studies

Alpha-Synuclein PFF Model

The PFF model uses synthetic preformed fibrils to induce endogenous α-synuclein aggregation.

• [Alpha-Synuclein PFF Model](/models/alpha-synuclein-pff-model)
• Mechanism: Prion-like seeding of endogenous α-synuclein
• Applications: Propagation studies, immunotherapy testing

LRRK2 Models

LRRK2 transgenic models express the G2019S mutation, the most common familial PD variant.

• [LRRK2 G2019S Transgenic Mouse Model](/models/lrrk2-g2019s-transgenic-mouse-model)
• Mechanism: Kinase hyperactivation (2-3x)
• Applications: LRRK2 kinase inhibitor testing
• [AAV-LRRK2 Gene Delivery Model](/models/aav-lrrk2-gene-delivery-model)
• Mechanism: Viral vector-mediated LRRK2 overexpression
• Applications: Regional overexpression, dose control

MitoPark Mouse Model

MitoPark uses tissue-specific Parkin deletion to model mitochondrial dysfunction in PD.

• [MitoPark Mouse Model](/models/mitopark-mouse-model)
• Mechanism: Impaired mitophagy leads to mitochondrial dysfunction
• Applications: Mitophagy enhancers, mitochondrial protectants

Rotenone-Induced Parkinsonism Model

Rotenone is a complex I inhibitor that reproduces mitochondrial dysfunction and α-synuclein pathology.

• [Rotenone-Induced Parkinsonism Model](/models/rotenone-parkinsonism-model)
• Mechanism: Chronic complex I inhibition
• Applications: Mitochondrial therapies, neuroprotection

Human Cell Models

iPSC-Derived Dopaminergic Neurons

Induced pluripotent stem cell-derived neurons provide patient-specific disease modeling.

• [iPSC-Derived Dopaminergic Neurons](/models/ipsc-derived-dopaminergic-neurons)
• Mechanism: Patient-derived neurons reveal disease phenotypes
• Applications: Drug screening, personalized medicine

All Model Pages (13 total)

| Model | Disease | Species | Key Applications |
|-------|---------|---------|-----------------|
| [5xFAD](/models/5xfad-transgenic-mouse-model) | Alzheimer's | Mouse | Amyloid, immunotherapy |
| [APP/PS1](/models/app-ps1-dual-transgenic-model) | Alzheimer's | Mouse | Amyloid, biomarkers |
| [Cerebral Organoid](/models/cerebral-organoid-model) | AD/PD | Human | 3D modeling, drug testing |
| [6-OHDA Rat](/models/6-ohda-rat-model-parkinsons) | Parkinson's | Rat | Motor deficits, cell therapy |
| [MPTP Mouse](/models/mptp-mouse-model-parkinsons) | Parkinson's | Mouse | Neuroprotection |
| [A53T α-Syn](/models/a53t-alpha-synuclein-mouse-parkinsons) | Parkinson's | Mouse | Aggregation |
| [A30P α-Syn](/models/a30p-alpha-synuclein-mouse-model) | Parkinson's | Mouse | Aggregation |
| [α-Syn PFF](/models/alpha-synuclein-pff-model) | Parkinson's | Mouse | Prion-like propagation |
| [LRRK2 G2019S](/models/lrrk2-g2019s-transgenic-mouse-model) | Parkinson's | Mouse | Kinase inhibitors |
| [AAV-LRRK2](/models/aav-lrrk2-gene-delivery-model) | Parkinson's | Mouse | Gene delivery |
| [MitoPark](/models/mitopark-mouse-model) | Parkinson's | Mouse | Mitochondrial |
| [Rotenone](/models/rotenone-parkinsonism-model) | Parkinson's | Rat | Mitochondrial |
| [iPSC DA Neurons](/models/ipsc-derived-dopaminergic-neurons) | Parkinson's | Human | Drug screening |

Related Sections

• [Experiments](/experiments) — Experimental methods and protocols
• [Therapeutics](/therapeutics) — Therapeutic interventions tested in models
• [Mechanisms](/mechanisms) — Disease mechanisms studied in model systems

Page Count

Total: 15 model pages

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Nutrient-Sensing Epigenetic Circuit Reactivation](/hypothesis/h-4bb7fd8c) — <span style="color:#81c784;font-weight:600">0.79</span> · Target: SIRT1
• [CYP46A1 Overexpression Gene Therapy](/hypothesis/h-2600483e) — <span style="color:#81c784;font-weight:600">0.79</span> · Target: CYP46A1
• [Selective Acid Sphingomyelinase Modulation Therapy](/hypothesis/h-de0d4364) — <span style="color:#81c784;font-weight:600">0.77</span> · Target: SMPD1
• [Microbial Inflammasome Priming Prevention](/hypothesis/h-e7e1f943) — <span style="color:#81c784;font-weight:600">0.76</span> · Target: NLRP3, CASP1, IL1B, PYCARD
• [TREM2-Dependent Microglial Senescence Transition](/hypothesis/h-61196ade) — <span style="color:#81c784;font-weight:600">0.76</span> · Target: TREM2
• [Blood-Brain Barrier SPM Shuttle System](/hypothesis/h-959a4677) — <span style="color:#81c784;font-weight:600">0.75</span> · Target: TFRC
• [Purinergic Signaling Polarization Control](/hypothesis/h-0758b337) — <span style="color:#81c784;font-weight:600">0.74</span> · Target: P2RY1 and P2RX7
• [SASP-Mediated Complement Cascade Amplification](/hypothesis/h-58e4635a) — <span style="color:#81c784;font-weight:600">0.73</span> · Target: C1Q/C3

Related Analyses:

• [TDP-43 phase separation therapeutics for ALS-FTD](/analysis/SDA-2026-04-01-gap-006) &#x1f504;
• [Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)](/analysis/SDA-2026-04-02-gap-seaad-v4-20260402065846) &#x1f504;
• [SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas](/analysis/analysis-SEAAD-20260402) &#x1f504;