APP and Alzheimer disease: In this study, we developed a mechanistic model of Alzheimer's Disease progression (mAD) that integrates amyloid precursor protein (APP) processing, Aβ peptide generation, Aβ aggregation pathway modeling, Aβ transport, and whole-body biomarker kinetics (BxK) of Aβ<sub>40</sub> and Aβ<sub>42</sub> peptides, including enzymatic and microglial clearance mechanisms.