Advances in the development paradigm of biosample‐based biosensors for early ultrasensitive detection of alzheimer’s disease

Abstract

This review highlights current developments, challenges, and future directions for the use of invasive and noninvasive biosample-based small biosensors for early diagnosis of Alzheimer’s disease (AD) with biomarkers to incite a conceptual idea from a broad number of readers in this field. We provide the most promising concept about biosensors on the basis of detection scale (from femto to micro) using invasive and noninvasive biosamples such as cerebrospinal fluid (CSF), blood, urine, sweat, and tear. It also summarizes sensor types and detailed analyzing techniques for ultrasensitive detection of multiple target biomarkers (i.e., amyloid beta (Aβ) peptide, tau protein, Acetylcholine (Ach), microRNA137, etc.) of AD in terms of detection ranges and limit of detections (LODs). As the most significant disadvantage of CSF and blood-based detection of AD is associated with the invasiveness of sample collection which limits future strategy with home-based early screening of AD, we extensively reviewed the future trend of new noninvasive detection techniques (such as optical screening and bio-imaging process). To overcome the limitation of non-invasive biosamples with low concentrations of AD biomarkers, current efforts to enhance the sensitivity of biosensors and discover new types of biomarkers using non-invasive body fluids are presented. We also introduced future trends facing an infection point in early diagnosis of AD with simultaneous emergence of addressable innovative technologies.

Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer’s Disease in Blood

“…In AD, although cerebrospinal fluid biomarkers are the most well-researched and widely accepted, blood biomarkers show greater prospects in the diagnosis of AD. The widespread application of blood biomarkers relies on the development and application of ultra-sensitive detection methods ( Karki et al, 2021 ), so their accurate detection and quantification will greatly facilitate current and future diagnostic and therapeutic efforts. This review introduces the application of peptides or peptide mimics of different sources and functions as identification elements or carriers of biosensors or molecular probes in the highly sensitive detection and diagnosis of AD.…”

Plasma Core Alzheimer’s Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline

“…However, the relationships regrading Aβ40 and Aβ42/40 between plasma and CSF were not found in our study, which were inconsistent with the results of another study by Janelidze et al They demonstrated that Aβ40 and Aβ42/40 in plasma were also in slightly positive correlation with those in CSF. Besides the fact that the samples were of a limited size in our study, the most important reason was that the production and transport of plasma Aβ peptides were complicated and the measurement was interfered by in vivo and in vitro factors, , even with the ultrasensitive technology adopted.…”

Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives

“…There are some ways to solve these challenges (Table 1 ). First, developing ultrasensitive technologies could improve the detection ranges of plasma biomarkers, and newly-exploited antibodies are more specific and sensitive in capturing biomarkers [ 34 , 35 ]. Advanced methods for concentrating biomarkers in blood could also resolve the dilution effect.…”