A Novel Serum-Based Diagnosis of Alzheimer's Disease Using an Advanced Phage-Based Biochip

Adv Sci (Weinh). 2023 Jul;10(21):e2301650. doi: 10.1002/advs.202301650. Epub 2023 May 7.

Abstract

55 million people worldwide suffer from Alzheimer's disease (AD). A definitive diagnosis of AD is made postmortem after a neuropathological examination of the brain. There is an urgent need for an innovative, noninvasive methodology that allows for an early and reliable diagnosis. Several engineered phages that recognized Aβ-autoantibodies present in the sera of AD patients are previously identified. Here, novel phages are tested for their ability to accurately discriminate AD sera using immunophage-polymerase chain reaction in a miniatured biochip. It is found that five of the six phages analyzed discriminate between healthy controls and AD patients. Further, by combining the response of two phages, non-AD and severe AD cases are identified with 100% accuracy and mild-to-moderate cases with 90% accuracy. While the number of cases used here are relatively small and can be confirmed in larger cohorts, this first-of-a-kind system represents an innovative methodology with the potential of having a major impact in the AD field: from a clinical perspective, it can aid physicians in making an accurate AD diagnosis; from a research perspective, it can be used as a surrogate for AD clinical trials.

Keywords: A-beta; biomarker; biosensor; neurodegeneration; phage display.

MeSH terms

  • Alzheimer Disease* / diagnosis
  • Bacteriophages* / genetics
  • Biomarkers
  • Brain / pathology
  • Humans

Substances

  • Biomarkers