From reaction kinetics to dementia: A simple dimer model of Alzheimer’s disease etiology

 You'll want you doctors and hospital to follow this closely so that EXACT PREVENTION PROTOCOLS  can be created for your likely dementia.

Your risk of dementia, has your doctor told you of this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

The latest here:

From reaction kinetics to dementia: A simple dimer model of Alzheimer’s disease etiology

• Michael R. Lindstrom, 
• Manuel B. Chavez, 
• Elijah A. Gross-Sable, 
• Eric Y. Hayden, 
• David B. Teplow

• Published: July 19, 2021
• https://doi.org/10.1371/journal.pcbi.1009114
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Abstract

Oligomers of the amyloid β-protein (Aβ) have been implicated in the pathogenesis of Alzheimer’s disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomer-dimer-trimer kinetics to develop a simple mathematical model linking Aβ assembly to oligomer-induced neuronal degeneration. This model recapitulates the rapid growth of disease incidence with age. It does so through incorporation of age-dependent changes in rates of Aβ monomer production and elimination. The model also describes clinical progression in genetic forms of AD (e.g., Down’s syndrome), changes in hippocampal volume, AD risk after traumatic brain injury, and spatial spreading of the disease due to foci in which Aβ production is elevated. Continued incorporation of clinical and basic science data into the current model will make it an increasingly relevant model system for doing theoretical calculations that are not feasible in biological systems. In addition, terms in the model that have particularly large effects are likely to be especially useful therapeutic targets.

Author summary

Oligomeric assemblies of Aβ are hypothesized to be seminal pathologic agents in Alzheimer’s disease (AD). Mechanistic studies of oligomerization and neurotoxicity in humans are currently impossible, yet such studies promise to advance efforts toward target identification and drug development. To overcome this hurdle, we developed a simple, mathematical model parameterized using experimental data extant. The model couples the kinetics of oligomerization with oligomer toxicity and enables determination of age-related changes in AD risk and hippocampal volume, the effects of traumatic brain injury on lifetime AD risk, gene dosage effects, and the effects of spatial variation in Aβ monomer concentrations on millimeter scales. The model is easily interpretable and provides a foundation for development of more comprehensive models of AD development and progression.

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Citation: Lindstrom MR, Chavez MB, Gross-Sable EA, Hayden EY, Teplow DB (2021) From reaction kinetics to dementia: A simple dimer model of Alzheimer’s disease etiology. PLoS Comput Biol 17(7): e1009114. https://doi.org/10.1371/journal.pcbi.1009114