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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. | 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. | ||
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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. We currently have an incredible wealth of detailed knowledge relevant to the disease. What's needed is a means to integrate this knowledge | 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. We currently have an incredible wealth of detailed knowledge relevant to the disease. What's needed is a means to integrate this knowledge to develop a more quantitative and rigorous science. | ||
== Alzheimer’s Disease Multiscale | == Alzheimer’s Disease Multiscale Modelling Project == | ||
This initiative develops '''mechanistic, quantitative models''' of Alzheimer’s disease that connect molecular processes to brain-level observables. | This initiative develops '''mechanistic, quantitative models''' of Alzheimer’s disease that connect molecular processes to brain-level observables. | ||
Revision as of 13:23, 28 February 2026
Let's work together to unravel the mystery of Alzheimer's Disease.
"A full comprehension of the causes of a deadly disease is the essential prerequisite to find a cure." [1] 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. We currently have an incredible wealth of detailed knowledge relevant to the disease. What's needed is a means to integrate this knowledge to develop a more quantitative and rigorous science.
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.
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
Explore the Methodological Framework →
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
View Multiscale Organization →
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 (Aβ Asp23Asn)
- London mutation
- Additional programs in development
See Active Modeling Programs →
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.
Read About Validation Methods →
Current Focus
Active modeling effort:
Mutation-specific aggregation kinetics (Iowa mutation) → scaling to predicted amyloid PET progression and age-of-onset shift.
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
This project aims to build cumulative, transparent, and quantitatively rigorous models of Alzheimer’s disease progression.
Getting started
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- Configuration settings list
- MediaWiki FAQ
- MediaWiki release mailing list
- Localise MediaWiki for your language
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Notes
- ↑ 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.