WikiMaladie - User contributions [en-gb]

Main Page

2026-03-15T11:35:29Z

RobAsWikiUser:

Advances biomedical science through integrating knowledge with quantitative models.

This project aims to formalize and connect existing knowledge into predictive, multiscale modelling frameworks that can be evaluated against measurable data.

== Mission ==
Our goal is to integrate biological knowledge through computational modeling
to understand disease mechanisms.

== Approach ==
* Integrate published knowledge
* Develop quantitative mechanistic models
* Compare predictions with observations

{| class="wikitable" style="background:#f8f9fa; border:1px solid #a2a9b1; padding:8px; width:85%;"
|-
| '''How to Contribute'''

Contributions are welcome from scientists with different backgrounds. Biologists and clinicians can help ensure that models remain grounded in experimental observations, while biophysicists and computational scientists can assist in translating mechanistic ideas into formal models.

Contributors are invited to contact the site's founder ([mailto:robert.scott@univ-brest.fr robert.scott@univ-brest.fr]) or edit the pages directly as on Wikipedia.
|}

== Disease Programs ==
* [[Alzheimer's Disease]]
* [[Carcinogenesis]]
* (future diseases)

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Main Page

2026-03-15T11:33:46Z

RobAsWikiUser:

= Wikimaladie =

== Mission ==
Our goal is to integrate biological knowledge through computational modeling
to understand disease mechanisms.

== Approach ==
* Integrate published knowledge
* Develop quantitative mechanistic models
* Compare predictions with observations

{| class="wikitable" style="background:#f8f9fa; border:1px solid #a2a9b1; padding:8px; width:85%;"
|-
| '''How to Contribute'''

Contributions are welcome from scientists with different backgrounds. Biologists and clinicians can help ensure that models remain grounded in experimental observations, while biophysicists and computational scientists can assist in translating mechanistic ideas into formal models.

Contributors are invited to contact the site's founder ([mailto:robert.scott@univ-brest.fr robert.scott@univ-brest.fr]) or edit the pages directly as on Wikipedia.
|}

== Disease Programs ==
* [[Alzheimer's Disease]]
* [[Carcinogenesis]]
* (future diseases)

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Main Page

2026-03-15T11:31:16Z

RobAsWikiUser:

== Mission ==
Our goal is to integrate biological knowledge through computational modeling
to understand disease mechanisms.

== Approach ==
* Integrate published knowledge
* Develop quantitative mechanistic models
* Compare predictions with observations

{| class="wikitable" style="background:#f8f9fa; border:1px solid #a2a9b1; padding:8px; width:85%;"
|-
| '''How to Contribute'''

Contributions are welcome from scientists with different backgrounds. Biologists and clinicians can help ensure that models remain grounded in experimental observations, while biophysicists and computational scientists can assist in translating mechanistic ideas into formal models.

Contributors are invited to contact the site's founder ([mailto:robert.scott@univ-brest.fr robert.scott@univ-brest.fr]) or edit the pages directly as on Wikipedia.
|}

== Disease Programs ==
* [[Alzheimer's Disease]]
* [[Carcinogenesis]]
* (future diseases)

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Alzheimer's Disease

2026-03-15T11:22:58Z

RobAsWikiUser: Created page with "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." <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 und..."

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."
<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.

----

=== 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 →]]

----

=== 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 →]]

----

=== 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 →]]

----

=== 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 →]]

----

=== 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

[[Collaboration|Contribution Guidelines →]]

----

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

Main Page

2026-03-15T11:20:39Z

RobAsWikiUser:

Iowa Mutation Modeling Program

2026-02-28T21:05:34Z

RobAsWikiUser: Created page with "== Iowa Mutation Modeling Program == '''Mutation:''' Aβ Asp23Asn '''Objective:''' Determine whether mutation-specific changes in aggregation kinetics are sufficient to explain altered amyloid deposition patterns and clinical onset timing. ---- === 1. Biological Background === ==== 1.1 Genetic and Molecular Context ==== * Description of the Asp23Asn substitution * Location within Aβ sequence * Known biochemical effects (e.g., altered charge, isomerization propensit..."

== Iowa Mutation Modeling Program ==
'''Mutation:''' Aβ Asp23Asn
'''Objective:''' Determine whether mutation-specific changes in aggregation kinetics are sufficient to explain altered amyloid deposition patterns and clinical onset timing.

----

=== 1. Biological Background ===

==== 1.1 Genetic and Molecular Context ====
* Description of the Asp23Asn substitution
* Location within Aβ sequence
* Known biochemical effects (e.g., altered charge, isomerization propensity)

==== 1.2 Reported Phenotypic Features ====
* Age of onset distribution
* Neuropathological characteristics
* Reported fibril properties
* Relevant clinical observations

----

=== 2. Working Mechanistic Hypothesis ===

Precise statement of the causal claim under investigation.

Example structure:

* The Asp23Asn mutation alters local electrostatic interactions.
* This increases fibril thermodynamic stability.
* Increased stability modifies aggregation kinetics (nucleation, elongation, secondary nucleation).
* Altered kinetics propagate to macroscopic plaque accumulation dynamics.

Clearly distinguish:
* Assumptions
* Empirical constraints
* Open uncertainties

----

=== 3. Mathematical Formalization ===

==== 3.1 Aggregation Kinetics Model ====
* Governing equations (e.g., nucleation–elongation framework)
* Definition of state variables
* Rate constants
* Conservation constraints

==== 3.2 Mutation-Specific Modifications ====
* Which parameters differ from wild-type?
* Justification for parameter changes
* Sensitivity to parameter variation

==== 3.3 Assumptions and Simplifications ====
* Spatial homogeneity vs heterogeneity
* Deterministic vs stochastic treatment
* Boundary conditions

----

=== 4. Parameterization ===

Structured parameter table:

{| class="wikitable"
! Parameter !! Symbol !! Value !! Source !! Experimental Context
|-
| Primary nucleation rate || k_n || ... || ... || in vitro aggregation assay
|-
| Elongation rate || k_+ || ... || ... || ...
|-
| Secondary nucleation rate || k_2 || ... || ... || ...
|}

Include:
* Units
* Measurement uncertainty
* Scaling assumptions (in vitro → in vivo)

----

=== 5. Scaling Strategy ===

How molecular kinetics propagate upward.

==== 5.1 From Aggregates to Plaque Load ====
* Mapping monomer/polymer concentration to plaque mass
* Spatial assumptions

==== 5.2 From Plaque Load to Imaging Signal ====
* Relationship to PET SUVR
* Assumed conversion functions

==== 5.3 From Plaque Accumulation to Clinical Onset ====
* Threshold hypotheses
* Network vulnerability assumptions

Explicitly state which links are empirical vs theoretical.

----

=== 6. Quantitative Predictions ===

Clearly enumerated, falsifiable predictions:

* Predicted shift in age of detectable amyloid PET signal
* Predicted plaque growth rate differences vs wild-type
* Predicted regional deposition differences
* Sensitivity of onset timing to kinetic parameters

Avoid vague language. Use numerical ranges where possible.

----

=== 7. Comparison with Existing Data ===

* PET studies in Iowa mutation carriers
* Reported onset ages
* Neuropathological findings

Explicitly state:
* Agreement
* Discrepancies
* Unexplained features

----

=== 8. Sensitivity and Identifiability Analysis ===

* Which parameters dominate model behavior?
* Are multiple parameter combinations indistinguishable?
* Which measurements would most constrain uncertainty?

This section signals modeling seriousness.

----

=== 9. Open Problems ===

* Missing kinetic measurements
* In vivo vs in vitro scaling uncertainties
* Spatial heterogeneity
* Interaction with tau pathology

----

=== 10. Next Steps ===

* Required data
* Computational refinement
* Proposed experimental collaborations

Main Page

2026-02-28T13:26:56Z

RobAsWikiUser:

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."
<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.

This project aims to formalize and connect existing knowledge into predictive, multiscale frameworks that can be evaluated against measurable data.

== 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

[[Methodological Framework|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

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

[[Familial Alzheimer’s Modeling|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.

[[Validation Framework|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

[[Collaboration|Contribution Guidelines →]]

----

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

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Main Page

2026-02-28T13:23:24Z

RobAsWikiUser:

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."
<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. 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

[[Methodological Framework|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

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

[[Familial Alzheimer’s Modeling|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.

[[Validation Framework|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

[[Collaboration|Contribution Guidelines →]]

----

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

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Main Page

2026-02-28T13:11:59Z

RobAsWikiUser:

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."
<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. We currently have an incredible wealth of detailed knowledge relevant to the disease. What's needed is a means to integrate this knowledge in develop a quantitative and rigorous science.
== Alzheimer’s Disease Multiscale Modeling 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

[[Methodological Framework|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

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

[[Familial Alzheimer’s Modeling|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.

[[Validation Framework|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

[[Collaboration|Contribution Guidelines →]]

----

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

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

==Notes==
<references />

Hypotheses about the primary origin

2026-01-09T09:37:34Z

RobAsWikiUser:

Here we collect primary origin hypotheses.

In 1987, a link between herpes simplex virus and Alzheimer's Disease was proposed.
<ref>
Behl, Christian. Alzheimer’s Disease Research: What Has Guided Research So Far and Why It Is High Time for a Paradigm Shift. Chapter 8. Springer International Publishing. Kindle Edition.
</ref>

Hypotheses about the primary origin

2026-01-09T09:36:07Z

RobAsWikiUser: Created page with "Here we collect primary origin hypotheses. In 1987, a link between herpes simplex virus and Alzheimer's Disease was proposed."

Here we collect primary origin hypotheses.

In 1987, a link between herpes simplex virus and Alzheimer's Disease was proposed.

Main Page

2026-01-09T09:28:41Z

RobAsWikiUser:

Main Page

2026-01-09T09:25:57Z

RobAsWikiUser:

Main Page

2025-12-06T05:51:04Z

RobAsWikiUser:

Main Page

2025-12-06T05:14:25Z

RobAsWikiUser:

Main Page

2025-12-05T09:26:28Z

RobAsWikiUser:

Non-primary mechanism hypotheses

2025-12-05T09:24:04Z

RobAsWikiUser: Created page with "There are many non-primary mechanism hypotheses. These are hypotheses about pathologies that are important for the development of the disease but are not the primary cause that started the causal chain of events that led to the disease. The amyloid beta cascade hypothesis."

There are many non-primary mechanism hypotheses. These are hypotheses about pathologies that are important for the development of the disease but are not the primary cause that started the causal chain of events that led to the disease.

The amyloid beta cascade hypothesis.

Main Page

2025-12-05T09:13:36Z

RobAsWikiUser:

Let's work together to unravel the mystery of Alzheimer's Disease.

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 many hypotheses about potentially relevant mechanisms in a causal chain, but it should be emphasized that we have no hypothesis about the primary origin. Let's call the former [[non-primary mechanism hypotheses]] to be clear on this point.

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

Main Page

2025-12-05T09:00:10Z

RobAsWikiUser:

Let's work together to unravel the mystery of Alzheimer's Disease.

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 many hypotheses about potentially relevant mechanisms in a causal chain, but it should emphasized that we have no hypothesis about the primary origin. Let's call the former [[non-primary mechanism hypotheses]] to be clear on this point.

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]

Main Page

2025-12-05T08:42:26Z

RobAsWikiUser: Setting up the main entry point to Wikimaladie.

Let's work together to unravel the mystery of Alzheimer's Disease.

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 many hypotheses about potentially relevant mechanisms, but it should emphasized that we have no hypothesis about the primary origin.

== Getting started ==
WikiMaladie uses MediaWiki, the same software that runs WikiPedia.
Consult the [https://www.mediawiki.org/wiki/Special:MyLanguage/Help:Contents User's Guide] for information on using the wiki software.
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Configuration_settings Configuration settings list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:FAQ MediaWiki FAQ]
* [https://lists.wikimedia.org/postorius/lists/mediawiki-announce.lists.wikimedia.org/ MediaWiki release mailing list]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Localisation#Translation_resources Localise MediaWiki for your language]
* [https://www.mediawiki.org/wiki/Special:MyLanguage/Manual:Combating_spam Learn how to combat spam on your wiki]