Elevated Aβ aggregates in feces from Alzheimer's disease patients: a proof-of-concept study

Alzheimers Res Ther. 2024 Oct 14;16(1):223. doi: 10.1186/s13195-024-01597-3.

Abstract

Background: Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer's disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut.

Methods: To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC).

Results: Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%).

Conclusion: Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated.

Keywords: Amyloidosis; Aβ oligomer quantitation; Brain-gut-microbiota axis; Clearance; Fecal/stool samples; Leaky gut; sFIDA.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides* / metabolism
  • Biomarkers / metabolism
  • Feces* / chemistry
  • Female
  • Humans
  • Male
  • Middle Aged
  • Proof of Concept Study
  • Protein Aggregates

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Protein Aggregates