Alzheimer Disease-Associated Gene Linked With Retinal Microvasculature Alterations

Optical Coherence Tomography (OCT)
Optical Coherence Tomography (OCT)
OCT and OCT-A may have the potential to be used as screening tools to identify asymptomatic, cognitively intact individuals at risk for developing Alzheimer’s Disease.

Apolipoprotein (APOE) ε4 allele (a gene linked with Alzheimer Disease) carriers are associated with decreased central subfield thickness (CST), perfusion density (PD), and peripapillary capillary flux index (CFI), according to a 2-year longitudinal study published in Ophthalmology Retina.

Researchers evaluated 413 eyes of 218 participants (age 55 years and older) with normal cognition and known APOE status (98 ε4 carriers, 120 non-carriers). They performed optical coherence tomography (OCT) and OCT angiography (OCT-A) imaging at baseline and at 2 year follow-up. Exclusion criteria included diabetes mellitus, glaucoma, uncontrolled hypertension, vitreoretinal disease, and neurodegenerative disease.

Baseline analysis revealed lower CST, PD in the 6mm Early Treatment Diabetic Retinopathy Study (ETDRS) circle, and temporal CFI measurements among APOE ε4 carriers compared with those who did not carry the gene (263 vs 268.8 µm, P =.018; 0.43 vs 0.34, P =.049; and 0.39 vs 0.41, P =.047, respectively). 

At follow-up, researchers noted that ε4 carriers had lower PD in the 6mm ETDRS circle (P =.05) and outer ring (P =.049), with no differences in rates of change between groups (all P >.05). While there was no significant difference in ganglion cell-inner plexiform layer (GC-IPL) or retinal nerve fiber layer (RNFL) thickness (P >.05 for both), the average GC-IPL thickness demonstrated a negative rate of change in the APOE ε4 group compared with no decline among controls.

Investigators acknowledge “measured differences in CST, PD, and peripapillary CFI between APOE ε4 carriers and non-carriers with normal cognition,” and believe that OCT and OCT-A may have the potential to serve as a screening tool for asymptomatic, cognitively intact individuals at risk for developing Alzheimer Disease. 

Study limitations include the lack of male representation and racial diversity among the cohort, the exclusion of younger individuals, and a high dropout rate due to the COVID-19 pandemic


Ma JP, Robbins CB, Lee JM, et al. Longitudinal analysis of the retina and choroid in cognitively normal individuals at higher genetic risk for Alzheimer disease. Ophthalmol Retina. Published online March 11, 2022. doi:10.1016/j.oret.2022.03.001