Alzheimer’s disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aβ), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from the amyloid precursor protein (APP), are the leading biomarkers for accurate and early diagnosis of AD due to their central role in disease pathology, their correlation with disease progression, their diagnostic value, and their implications for therapeutic interventions. Their detection and monitoring contribute significantly to understanding AD and advancing clinical care. Available diagnostic techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are mainly used to validate AD diagnosis. However, these methods are expensive, yield results that are difficult to interpret, and have common side effects such as headaches, nausea, and vomiting. Therefore, researchers have focused on developing cost-effective, portable, and point-of-care alternative diagnostic devices to detect specific biomarkers in cerebrospinal fluid (CSF) and other biofluids. In this review, we summarized the recent progress in developing electrochemical immunosensors for detecting AD biomarkers (Aβ and p-tau protein) and their subtypes (AβO, Aβ_(1-40), Aβ_(1-42), t-tau, cleaved-tau (c-tau), p-tau₁₈₁, p-tau₂₃₁, p-tau₃₈₁, and p-tau₄₄₁). We also evaluated the key characteristics and electrochemical performance of developed immunosensing platforms, including signal interfaces, nanomaterials or other signal amplifiers, biofunctionalization methods, and even primary electrochemical sensing performances (i.e., sensitivity, linear detection range, the limit of detection (LOD), and clinical application).

Metabolites are essential molecules involved in various metabolic processes, and their deficiencies and excessive concentrations can trigger significant physiological consequences. The detection of multiple metabolites within a non‐invasively collected biofluid could facilitate early prognosis and diagnosis of severe diseases. Here, a metal oxide heterojunction transistor (HJ‐TFT) sensor is developed for the label‐free, rapid detection of uric acid (UA) and 25(OH)Vitamin‐D3 (Vit‐D3) in human saliva. The HJ‐TFTs utilize a solution‐processed In₂O₃/ZnO channel functionalized with uricase enzyme and Vit‐D3 antibody for the selective detection of UA and Vit‐D3, respectively. The ultra‐thin tri‐channel architecture facilitates strong coupling between the electrons transported along the buried In₂O₃/ZnO heterointerface and the electrostatic perturbations caused by the interactions between the surface‐immobilized bioreceptors and target analytes. The biosensors can detect a wide range of concentrations of UA (from 500 nm to 1000 µM) and Vit‐D3 (from 100 pM to 120 nm) in human saliva within 60 s. Moreover, the biosensors exhibit good linearity with the physiological concentration of metabolites and limit of detections of ≈152 nm for UA and ≈7 pM for Vit‐D3 in real saliva. The specificity is demonstrated against various interfering species, including other metabolites and proteins found in saliva, further showcasing its capabilities.