Alzheimer's disease (AD) is the sixth leading cause of death worldwide and is characterized by progressive and irreversible neurodegeneration. By the time clinical symptoms become apparent, extensive neural damage has already occurred, highlighting the critical need for early and sensitive detection of AD biomarkers. This review summarizes recent advances in non‐enzymatic electrochemical biosensor materials for detecting AD‐associated biomarkers in biofluids for early diagnosis. Key biomarkers implicated in AD onset and progression, including amyloid‐beta (Aβ) and hyperphosphorylated Tau (p‐Tau), are discussed, as their pathological aggregation disrupts neuronal signaling pathways. Electrochemical sensors are valuable tools due to their ultra‐low detection limits (femtomolar to picomolar), broad linear dynamic ranges (nanomolar to micromolar), and high analytical sensitivity. Equally important is their selectivity toward clinically relevant concentrations of Aβ and p‐Tau in complex biofluids such as cerebrospinal fluid (CSF) and blood. This review provides a discussion of materials‐driven, non‐enzymatic electrochemical sensing approaches, offering a critical assessment of their performance, selectivity, and translational challenges in minimally invasive biofluids, an area that continues to be insufficiently addressed in current AD biosensing research. Despite significant progress, the development of low‐cost, non‐enzymatic electrochemical sensors compatible with alternative, minimally invasive biofluids, including urine and saliva, remains limited, underscoring a key challenge and opportunity for next‐generation AD diagnostics.
Ting et al. (Fri,) studied this question.