Early Detection of Amyloidopathy in Alzheimer's Mice by Hyperspectral Endoscopy

Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3231-8. doi: 10.1167/iovs.15-17406.


Purpose: To describe a spectral imaging system for small animal studies based on noninvasive endoscopy of the retina, and to present time-resolved spectral changes from live Alzheimer's mice prior to cognitive decline, corroborating our previous in vitro findings.

Methods: Topical endoscope fundus imaging was modified to use a machine vision camera and tunable wavelength system for acquiring monochromatic images across the visible to near-infrared spectral range. Alzheimer's APP/PS1 mice and age-matched, wild-type mice were imaged monthly from months 3 through 8 to assess changes in the fundus reflection spectrum. Optical changes were fit to Rayleigh light scatter models as measures of amyloid aggregation.

Results: Good quality spectral images of the central retina were obtained. Short-wavelength reflectance from Alzheimer's mice retinae showed significant reduction over time compared to wild-type mice. Optical changes were consistent with an increase in Rayleigh light scattering in neural retina due to soluble Aβ1-42 aggregates. The changes in light scatter showed a monotonic increase in soluble amyloid aggregates over a 6-month period, with significant build up occurring at 7 months.

Conclusions: Hyperspectral imaging technique can be brought inexpensively to the study of retinal changes caused by Alzheimer's disease progression in live small animals. A similar previous finding of reduction in the light reflection over a range of wavelengths in isolated Alzheimer's mice retinae, was reproducible in the living Alzheimer's mice. The technique presented here has a potential for development as an early Alzheimer's retinal diagnostic test in humans, which will support the treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / diagnosis
  • Amyloidosis / complications
  • Amyloidosis / diagnosis*
  • Animals
  • Diagnosis, Differential
  • Disease Models, Animal
  • Early Diagnosis*
  • Endoscopy / methods*
  • Follow-Up Studies
  • Fundus Oculi
  • Mice
  • Mice, Transgenic
  • Reproducibility of Results
  • Retina / diagnostic imaging*
  • Retinal Diseases / diagnosis*
  • Retinal Diseases / etiology