Alzheimer's Disease Diagnosis in the Preclinical Stage: Normal Aging or Dementia

Alzheimer's disease (AD) progressively impairs the memory and thinking skills of patients, resulting in a significant global economic and social burden each year. However, diagnosis of this neurodegenerative disorder can be challenging, particularly in the early stages of developing cognitive decline. Current clinical techniques are expensive, laborious, and invasive, which hinders comprehensive studies on Alzheimer's biomarkers and the development of efficient devices for Point-of-Care testing (POCT) applications. To address these limitations, researchers have been investigating various biosensing techniques. Unfortunately, these methods have not been commercialized due to several drawbacks, such as low efficiency, reproducibility, and the lack of accurate identification of AD markers. In this review, we present diverse promising hallmarks of Alzheimer's disease identified in various biofluids and body behaviors. Additionally, we thoroughly discuss different biosensing mechanisms and the associated challenges in disease diagnosis. In each context, we highlight the potential of realizing new biosensors to study various features of the disease, facilitating its early diagnosis in POCT. This comprehensive study, focusing on recent efforts for different aspects of the disease and representing promising opportunities, aims to conduct the future trend toward developing a new generation of compact multipurpose devices that can address the challenges in the early detection of AD.