Fluid biomarkers in Alzheimer disease

Cold Spring Harb Perspect Med. 2012 Sep 1;2(9):a006221. doi: 10.1101/cshperspect.a006221.

Abstract

Research progress has provided detailed understanding of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new drug candidates with putative disease-modifying effects, which are now being tested in clinical trials. The promise of effective therapy has created a great need for biomarkers able to detect AD in the predementia phase, because drugs will probably be effective only if neurodegeneration is not too advanced. In this chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of β-amyloid (Aβ42) reflect AD pathology, and have high diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild cognitive impairment cases. The rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Amyloid Precursor Protein Secretases / cerebrospinal fluid
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Aspartic Acid Endopeptidases / cerebrospinal fluid
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Biomarkers, Pharmacological / blood
  • Biomarkers, Pharmacological / cerebrospinal fluid
  • Cerebrospinal Fluid Proteins / metabolism*
  • Humans
  • Isomerism
  • Isotope Labeling / methods
  • Neuritis / diagnosis
  • Neurofilament Proteins / cerebrospinal fluid
  • Neurofilament Proteins / metabolism
  • Oxidative Stress / physiology
  • Phosphorylation
  • tau Proteins / blood
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Biomarkers, Pharmacological
  • Cerebrospinal Fluid Proteins
  • Neurofilament Proteins
  • tau Proteins
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human