Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and neuronal dysfunction. Early diagnosis is critical for improving patient outcomes, yet current detection methods remain limited in sensitivity and accessibility. Platelet-derived growth factor receptor beta (PDGFR-β), a biomarker linked to blood–brain barrier integrity and neurovascular dysfunction, has emerged as a promising target for early AD detection. In this study, we employed an in silico approach to design and evaluate aptamers with high binding affinity for PDGFR-β. Protein structures were modeled using UniProt and AlphaFold, and potential binding sites were predicted with ScanNet, identifying the D2 extracellular domain as the most favorable target. Molecular docking simulations were performed with HDOCK, followed by detailed interaction profiling using PLIP and RinMaker. Binding free energies were calculated with PRODIGY to assess thermodynamic stability. The results demonstrated stable interactions, including hydrogen bonding, hydrophobic contacts, and salt bridges, with favorable ΔG values supporting strong aptamer–protein binding. These findings highlight the feasibility of computationally designed aptamers as diagnostic probes for PDGFR-β, providing a cost-effective and rapid approach for early-phase research. While experimental validation is required to confirm specificity and stability in biological systems, this work establishes a foundation for aptamer-based biosensors and diagnostic assays aimed at enabling earlier detection of AD.