Editing Alzheimer's Disease

<strong>Let's work together to unravel the mystery of Alzheimer's Disease.</strong>

"A full comprehension of the causes of a deadly disease is the essential prerequisite to find a cure."
<ref>
Behl, Christian. Alzheimer’s Disease Research: What Has Guided Research So Far and Why It Is High Time for a Paradigm Shift (p. 6). Springer International Publishing. Kindle Edition. 
</ref>
To find a cure for the disease, to find a disease changing medication, we must first understand the causal mechanisms at the origins of the disease, the aetiology. 
Over decades, an extensive body of experimental and clinical knowledge has been accumulated across molecular, cellular, and systems levels. What remains limited is the quantitative integration of these findings into mechanistically consistent, testable models.




== Alzheimer’s Disease Multiscale Modelling Project ==

This initiative develops '''mechanistic, quantitative models''' of Alzheimer’s disease that connect molecular processes to brain-level observables.

Biological hypotheses are formalized mathematically, parameterized using published experimental data, and propagated across biological scales. Model predictions are evaluated against imaging, biomarker, neuropathological, and clinical measurements.

The project operates as an open, technically rigorous modeling laboratory.

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=== Research Program ===

We convert mechanistic hypotheses into testable, quantitative predictions.

* Define biological mechanisms precisely  
* Express them in mathematical form  
* Constrain parameters using experimental literature  
* Scale effects from molecular to brain-level dynamics  
* Compare predictions with independent datasets  

[[Methodological Framework|Explore the Methodological Framework →]]

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=== Multiscale Structure of Alzheimer’s Disease ===

Alzheimer’s disease spans interacting biological levels. Our modeling framework is organized accordingly:

* '''Molecular Level''' – Aβ aggregation kinetics, mutation-specific effects  
* '''Cellular Level''' – Synaptic dysfunction, proteostasis disruption  
* '''Network Level''' – Connectivity degradation, propagation dynamics  
* '''Brain Level''' – Imaging biomarkers, regional atrophy patterns  
* '''Clinical Level''' – Cognitive decline trajectories  

[[Multiscale Organization|View Multiscale Organization →]]

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=== Strategic Focus: Familial Alzheimer’s Disease ===

Initial efforts focus on genetically defined forms of Alzheimer’s disease.

Familial mutations provide:

* Clear causal perturbations  
* Reduced biological heterogeneity  
* Stronger mechanistic constraints  

Active mutation-specific modeling programs include:

* [[Iowa Mutation Modeling Program|Iowa mutation (Aβ Asp23Asn)]]  
* [[London Mutation Modeling Program|London mutation]]  
* Additional programs in development  

[[Familial Alzheimer’s Modeling|See Active Modeling Programs →]]

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=== Model Validation Framework ===

Models are evaluated against multiple independent observables:

* CSF biomarker trajectories  
* Amyloid PET progression  
* Structural MRI atrophy  
* Longitudinal cognitive decline  
* Neuropathological findings  

Predictions must be quantitatively testable and reproducible.

[[Validation Framework|Read About Validation Methods →]]

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=== Current Focus ===

'''Active modeling effort:'''

Mutation-specific aggregation kinetics (Iowa mutation) → scaling to predicted amyloid PET progression and age-of-onset shift.

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=== Collaboration ===

Technically serious collaboration is welcome in:

* Mathematical and computational modeling  
* Parameter extraction from experimental literature  
* Dataset integration and harmonization  
* Independent validation and replication  
* Critical evaluation of model assumptions  

[[Collaboration|Contribution Guidelines →]]

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''This project aims to build cumulative, transparent, and quantitatively rigorous models of Alzheimer’s disease progression.''