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

Abstract

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer’s disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an “X” to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?

“…Even so, in this scheme, not all of the pathologies and related biomarkers are included. Therefore, Huang et al (2022) suggested adding an X to form the A-T-N-X framework, focusing on the CNS and periphery biomarkers associated with inflammation, systemic immunity, metabolism, and synaptic damage, neuroinflammation, glial cells. In the midto-long-term future, these frameworks should be validated in many clinical trials.…”

Biomarkers for the Diagnosis of Alzheimer’s Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria

“…The addition of the X category to the ATN framework allows for a better understanding of other pathologies and dynamic changes with the development of AD [ 67 ]. Huang et al proposed division by the X category for two subcategories, which could better reflect a whole spectrum of pathology in the central nervous system (CSN) and in periphery [ 68 ]. In , authors focused on biomarkers related to synaptic damage, glial cells, neuroinflammation, and immunity, whereas in , they focused on biomarkers associated with systemic immunity, inflammation, and metabolism [ 68 ].…”

“…Huang et al proposed division by the X category for two subcategories, which could better reflect a whole spectrum of pathology in the central nervous system (CSN) and in periphery [ 68 ]. In , authors focused on biomarkers related to synaptic damage, glial cells, neuroinflammation, and immunity, whereas in , they focused on biomarkers associated with systemic immunity, inflammation, and metabolism [ 68 ]. The above-mentioned studies confirmed that AD is a very complex and multifactorial neurodegenerative disease.…”

Dry Chemistry-Based Bipolar Electrochemiluminescence Immunoassay Device for Point-of-Care Testing of Alzheimer-Associated Neuronal Thread Protein

“…By the mid-21st century, the number of patients with dementia is predicted to reach 150 million, and the cost of treating, caring for, and managing these patients is estimated to be around 130 billion euros/year. , As a common type of dementia, Alzheimer’s disease (AD) is a progressive neurodegenerative disease with slow and insidious onset, and patients always go through three periods: preclinical, mild cognitive impairment, and eventual dementia . The clinical features of AD, such as memory and cognitive deterioration, aphasia, apraxia, and personality and behavioral changes, are characterized as irreversible symptoms .…”