Advances and applications of fluids biomarkers in diagnosis and therapeutic targets of Alzheimer's disease

CNS Neurosci Ther. 2023 Aug;29(8):2060-2073. doi: 10.1111/cns.14238. Epub 2023 May 5.

Abstract

Aims: Alzheimer's disease (AD) is a neurodegenerative disease with challenging early diagnosis and effective treatments due to its complex pathogenesis. AD patients are often diagnosed after the appearance of the typical symptoms, thereby delaying the best opportunity for effective measures. Biomarkers could be the key to resolving the challenge. This review aims to provide an overview of application and potential value of AD biomarkers in fluids, including cerebrospinal fluid, blood, and saliva, in diagnosis and treatment.

Methods: A comprehensive search of the relevant literature was conducted to summarize potential biomarkers for AD in fluids. The paper further explored the biomarkers' utility in disease diagnosis and drug target development.

Results: Research on biomarkers mainly focused on amyloid-β (Aβ) plaques, Tau protein abnormal phosphorylation, axon damage, synaptic dysfunction, inflammation, and related hypotheses associated with AD mechanisms. Aβ42 , total Tau (t-Tau), and phosphorylated Tau (p-Tau), have been endorsed for their diagnostic and predictive capability. However, other biomarkers remain controversial. Drugs targeting Aβ have shown some efficacy and those that target BACE1 and Tau are still undergoing development.

Conclusion: Fluid biomarkers hold considerable potential in the diagnosis and drug development of AD. However, improvements in sensitivity and specificity, and approaches for managing sample impurities, need to be addressed for better diagnosis.

Keywords: Alzheimer's disease; biomarkers; blood; cerebral spinal fluid; saliva; treatment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / drug therapy
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Aspartic Acid Endopeptidases
  • Biomarkers / cerebrospinal fluid
  • Humans
  • Neurodegenerative Diseases*
  • Peptide Fragments / cerebrospinal fluid
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments