Advances in nanomaterial-based biomarker detection for neurodegenerative diseases: Special focus on Alzheimer's and Parkinson's disease.

Amyloid-β aggregation, tau hyperphosphorylation, and α-synuclein misfolding are pathological processes that occur decades before clinical onset in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), but detection is still symptom based and technologically insufficient. Disease staging has been redefined by biomarker-centric frameworks, especially the AT(N) classification. However, low abundance, structurally heterogeneous biomarkers in complex biofluids are not resolved by current detection strategies because of limited sensitivity, matrix interference, and lack of conformational specificity. In this regard, nanomaterial enabled sensing platforms offer unique physicochemical properties: magnetic nanostructures enable background independent detection, carbon nanomaterials enable electrochemical signal amplification through improved charge transfer, and plasmonic nanostructures enable label-free optical detection via surface plasmon resonance. When combined, these systems allow for real-time analysis in physiologically relevant matrices, multiplexed detection, and femtomolar sensitivity. Despite advancements in analytical techniques, the practical application of these technologies is hindered by challenges such as biofouling, inconsistencies between batches, and a lack of adequate clinical validation. This review examines the potential of nanomaterial-based sensing strategies for developing clinically relevant neurodiagnostics, categorizes them systematically, and links them to biomarker profiles for AD and PD.