Biomarkers

Area of Science:

• Ophthalmology
• Neuroscience
• Gerontology

Background:

• Alzheimer's disease (AD) is characterized by reduced amyloid beta clearance, impacting glial cell function.
• Prior optical coherence tomography (OCT) studies indicated light-dependent retinal changes co-localizing with macroglia in later stages of AD.
• These glial function markers were subtly abnormal in advanced Alzheimer's disease.

Purpose of the Study:

• To investigate if similar light-dependent retinal changes occur in early-stage Alzheimer's disease, preceding structural alterations.
• To determine if Alzheimer's-associated functional abnormalities in the retina vary with proximity to the fovea.

Main Methods:

• Compared OCT images from early-stage Alzheimer's (ALZ) patients and biomarker-negative controls (CON).
• Measured macular and peripapillary retinal nerve fiber layer thicknesses.
• Collected functional data by imaging in darkness versus after bright light exposure, analyzing attenuation coefficient maps using multilevel models.

Main Results:

• While groups were age, sex, and education-balanced, ALZ patients had lower cognitive scores.
• A single structural difference: the central macula was thicker in ALZ.
• Both groups showed similar light responses in rod and cone outer segments, but significantly different functional responses in macroglia-occupied retinal layers, most robustly 0.5-1.0 mm from the foveal center.

Conclusions:

• Robust Alzheimer's-related functional changes are present in the retina at an earlier disease stage than previously identified.
• The location of these functional changes suggests a macroglial origin, rather than primarily neural or vascular.
• These findings highlight the retina as a potential site for early Alzheimer's disease detection.