Editing Iowa Mutation Modeling Program (section)

==== 2.4 Quantitative hypothesis: “surface-area amplification” ====
We translate the above into a quantitative causal chain:

(1) D23N increases the rate of isoAsp23 formation and/or stabilizes the fibril state.  
(2) Faster fibrillization and higher stability favor vascular/perivascular diffuse fibril deposition (CAA-associated “clouds”).  
(3) Diffuse fibrils yield higher total exposed fibril surface area per deposited mass than compact neuritic plaques.  
(4) Fibril surfaces catalyze oligomer generation (secondary nucleation / surface-catalyzed pathways).  
(5) If clearance is impaired (proteolysis resistance; limited repair; immune sink saturation), soluble oligomer concentration increases sufficiently to drive toxicity.

We treat steps (2)–(5) as a model to be constrained by data.

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