One of the primary challenges of diagnosing Alzheimer’s Disease (AD) lies in its progression through two silent decades. The lack of symptoms in patients during this time evidently hinders their chance of suspecting the disease, or merely being granted a precautionary brain scan. Moreover, the initial endogenous signs and noticeable symptoms often coincide with aging individuals without any neurological disease diagnosis. In the midst of these diagnostic challenges, fundamental and clinical research efforts have provided a sea of disparate information about the pathophysiology by tracing back the events that unfold with respect to small and large scale components. To capture the multifactorial nature of AD in the face of a heavily delayed diagnostic timeframe, it becomes intractable to attempt to account for the abundance of causal candidate factors for AD using standard analytical statistical techniques. 
Instead of tracing back AD signs and symptoms, we aim to simulate normal aging going forward in time, in the hopes of detecting more accurate early Alzheimer’s signs as they emerge, and subsequently diverge from typical aging-associated abnormalities. Therefore, we propose to restructure AD knowledge into several levels of abstraction or scales with the reliance on mathematical modeling techniques to represent AD more comprehensively, while inspiring the model from the process of normal aging from 18- to 100-year-old humans. 
We will conduct a thorough literature search to estimate parametric values required to satisfy our system of ordinary and partial differential equations, tailored to simulate normal aging. We will use an Agile approach to categorize entities known to play a role in aging such as 1) at the nanoscale with compounds like glucose and insulin, and proteins such as amyloid and tau; 2) at the microscale based on neuronal and glial populations as well as the vascular endothelium; 3) bringing them together to simulate and predict the trajectory of biomarkers at the mesoscale (e.g., neuronal integrity via cortical thickness, metabolic integrity via FDG-PET). The model’s use of estimated theoretical parameter values will in turn be validated with human data to orient its development in concordance with the longitudinal trajectory of the aging human.  
The multiscale hierarchy of neurological diseases which is composed of an incredibly complex interactome alarmingly prompt us to move on from single-component analyses, towards more carefully dissecting the most impactful entities, while adequately accounting for how they intertwine with each other during aging. This framework can provide a starting point for earlier detection of AD neurodegeneration and potentially facilitate the identification of more AD-specific pathways for future pharmacological interventions.