Beta-Amyloid Peptide in Tears: An Early Diagnostic Marker of Alzheimer's Disease Correlated with Choroidal Thickness

Int J Mol Sci. 2023 Jan 30;24(3):2590. doi: 10.3390/ijms24032590.

Abstract

We aimed to evaluate the diagnostic role of Alzheimer's disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, β-amyloid peptide Aβ1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aβ1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aβ1-42 were lower, both in the MCI (p < 0.01) and in the AD group (p < 0.001) when compared to healthy controls. Further, Aβ1-42 was correlated with psychometric scores (p < 0.001) and CT (p < 0.01). CT was thinner in the affected patients (p = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aβ1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

Keywords: APP; Alzheimer’s disease; beta-amyloid; biomarkers; choroidal thickness; p-tau; tears.

MeSH terms

  • Aged
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Cognitive Dysfunction*
  • Cross-Sectional Studies
  • Humans
  • Middle Aged
  • Peptide Fragments / metabolism
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • tau Proteins
  • Amyloid beta-Protein Precursor
  • Biomarkers

Grants and funding

The study was supported by the Sapienza University of Rome [grant number RG11916B795679B7/2019].