Parkinson’s disease (PD) lacks reliable biomarkers for early diagnosis, as current approaches depend on clinical symptoms that emerge only after extensive neurodegeneration. Aggregated α-synuclein (α-Syn), the pathological hallmark of PD, represents a promising biomarker, yet its low abundance and structural polymorphism hinder selective detection. Previous studies demonstrated that tetracyclines recognize the conserved cross-β motif present in toxic protein aggregates. Building on this, we developed a novel platform based on magnetic nanoparticles functionalized through biotinylation with tetracycline derivatives, designed to enhance both selectivity and sensitivity in the capture of α-Syn aggregates. Functional assays confirmed that the engineered nanoparticles preferentially bound aggregated α-Syn over its monomeric form, achieving robust discrimination under controlled in vitro conditions. The effective capture surface was markedly increased, leading to a substantial gain in sensitivity while the magnetic properties enabled efficient isolation and concentration of aggregated species, improving the signal-to-noise ratio. This dual advantage establishes the platform as a versatile biorecognition tool compatible with established ultrasensitive methods. These findings establish proof-of-concept for tetracycline-functionalized magnetic nanoparticles as a new generation of highly sensitive diagnostic platforms targeting α-Syn aggregates, with potential applications in PD.