Blood-based Biomarkers of Alzheimer’s Disease: The Long and Winding Road

Abstract

Background: Blood-based biomarkers can be very useful in formulating new diagnostic and treatment proposals in the field of dementia, especially in Alzheimer’s disease (AD). However, due to the influence of several factors on the reproducibility and reliability of these markers, their clinical use is still very uncertain. Thus, up-to-date knowledge about the main blood biomarkers that are currently being studied is extremely important in order to discover clinically useful and applicable tools, which could also be used as novel pharmacological strategies for the AD treatment. Objective: The aim of this paper was to carry out a literature review on the major blood-based biomarkers for AD, connecting them with the pathophysiology of the disease. Methods: A narrative review was performed based on the current candidates of blood-based biomarkers for AD to show the main results from different studies, focusing on their clinical applicability and association with AD pathogenesis. Results: Recent advances in the search of blood-based AD biomarkers were summarized in this review. The biomarkers were classified according to the topics related to the main hallmarks of the disease such as inflammation, amyloid, and tau deposition, synaptic degeneration and oxidative stress. Moreover, molecules involved in the regulation of proteins related to these hallmarks were described, such as non-coding RNAs, neurotrophins, growth factors and metabolites. Cells or cellular components with the potential to be considered as blood-based AD biomarkers were described in a separate topic. Conclusion: A series of limitations undermine new discoveries on blood-based AD biomarkers. The lack of reproducibility of findings due to the small size and heterogeneity of the study population, different analytical methods and other assay conditions make longitudinal studies necessary in this field to validate these structures, especially when considering a clinical evaluation that includes a broad panel of these potential and promising blood-based biomarkers.