Multiplex immunoassay measurement of amyloid-β42 to amyloid-β40 ratio in plasma discriminates between dementia due to Alzheimer's disease and dementia not due to Alzheimer's disease

Exp Brain Res. 2018 May;236(5):1241-1250. doi: 10.1007/s00221-018-5210-x. Epub 2018 Feb 26.

Abstract

The cerebrospinal fluid (CSF) biomarkers amyloid-β42 (Aβ42), total Tau, and phospho-181-Tau represent important diagnostic tools to support the clinical diagnosis of Alzheimer's disease (AD). Acquiring CSF by lumbar puncture is considered a moderately invasive procedure, while blood sampling is minimally invasive with calculable risks and can be performed by trained non-medical staff. Thus, the identification of reliable and robust blood biomarkers of AD-related neuropathology would be significantly advantageous in daily practice and would allow more patients to be screened. In this study, we performed a multiplex amyloid-β assay to simultaneously measure Aβ40 and Aβ42. We analyzed how well Aβ40, Aβ42, and the Aβ42 to Aβ40 ratio (Aβ42/40) could differentiate between patients suffering from dementia either due or not due to AD. In addition, we studied different factors affecting Aβ levels in plasma. Plasma Aβ42/40 level was significantly lower in patients with dementia due to AD than in those with dementia due to other causes. Aβ42/40 correlated weakly between plasma and CSF, but did not differ between amyloid-PET positive or negative patients. Furthermore, we found that kidney function influences Aβ40 and Aβ42 plasma levels, but not Aβ42/40 level. Liver function, age, and sex do not affect Aβ levels in plasma.

Keywords: Alzheimer’s disease; Amyloid-β; Assay validation; Biomarker; Dementia; Plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / blood*
  • Biomarkers / blood
  • Dementia / blood
  • Dementia / diagnosis*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunoassay / methods
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Sex Factors

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)