APOE Ɛ4 genotype is associated with thicker retinal layers in asymptomatic middle‐aged adults at high Alzheimer’s disease risk

Abstract

AbstractBackgroundRetinal abnormalities have been demonstrated in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD), but findings in yet asymptomatic stages of the disease are scarce and inconsistent. This study examined the relationship of retinal thickness with APOE Ɛ4 genotype, the most important genetic risk factor for AD.MethodParticipants (n=245) were cognitively asymptomatic middle aged people taking part in the Israel Registry for Alzheimer's Prevention (IRAP) study, enriched for high AD‐risk due to parental history of the disease. Assessments included a complete ophthalmic examination, best‐corrected visual acuity (BCVA) evaluation and optic coherence tomography (SD‐OCT) imagingAPOE status was determined based on rs429358 and rs7412 SNPs' genotypes. MANCOVA was used to compare retinal thickness between APOE Ɛ4 carriers and non‐carriers adjusting for age, sex, education and BCVA in four retinal quadrants (nasal, inferior, temporal and superior).ResultParticipants' mean age was 59.60 (SD=6.42) years, 66.4% were women. Retinal thickness was significantly greater in APOE Ɛ4 carriers compared to non‐carriers (p=0.005), reaching statistical significance in the nasal (p=0.008) and inferior (p=0.022) regions. A secondary MANCOVA analysis examined differences between APOE4 carriers and non‐carriers in specific retinal layers‐ the neural and glial layers (Retinal Nerve Fiber Layer‐ RNFL, Ganglion Cell Layer– GCL, Inner Plexiform Layer‐IPL, Inner Nuclear Layer‐INL and the Outer Plexiform Layer‐OPL) and the non‐neural layers (Outer Nuclear Layer‐ONL and the Retinal Pigment Epithelium (RPE). In the nasal region, APOE4 carriers had thicker retinal nerve fiber layer (RNFL) (p=0.033), ganglion cell layer (GCL) (p=0.021) and inner plexiform layer (IPL) (p=0.010); in the inferior region, they had thicker GCL (p=0.035); and in the superior region, the APOE4 carriers had thicker IPL (p=0.019).ConclusionIn asymptomatic individuals enriched for AD risk, APOE4 carriers had thicker retinal nasal and inferior quadrants, which were driven primarily by the neural layers of the retina, but not by non‐neural layers. Our results suggest that retinal layers' thickness measurments may potentially be used as early biomarkers the disease.