The retinal choroid as an oculovascular biomarker for Alzheimer's dementia: A histopathological study in severe disease

Abstract

Introduction: Previous in vivo optical coherence tomography studies have proposed the retinal choroid as a potential oculovascular biomarker for Alzheimer's disease (AD). However, the clinical use of the choroid as a purported surrogate marker remains poorly understood. We pursued a histopathological approach to assess choroidal thickness and vascular morphology in severe disease.

Methods: Human postmortem tissues from 8 patients with AD (mean age: 80.1 ± 12.7 years) and from 11 age-matched controls (mean age: 78.4 ± 16.57 years) were analyzed. Thickness, area, and vascularity of the retinal choroid and its sublayers were measured from the nasal and temporal quadrants of the superior retina.

Results: Nasally, the choroid was thinner in the patients with AD than in the controls (22% thickness reduction; P < .001), but to our surprise, the choroid was thicker in the patients with AD than in the controls (~60% increase; P < .03) within the macula, temporally. The choroidal area was also significantly greater in the patients with AD than in the controls (~60% increase; P < .03). Choroidal thickening in AD was strongly correlated with the stromal vessel number (R² = 0.96, P < .001).

Discussion: We found significant differences in the retinal choroid by layer and by region, nasally and temporally with respect to the optic nerve. Intriguingly, the choroid was markedly thicker in the central macular region and was strongly associated with vessel number in the stromal vascular layer. These quantified histological findings in severe disease expand our understanding of vascular pathology in AD and suggest vascularity as a potential biomarker supplementary to thickness when evaluating the retinal choroid in AD.

Keywords: Alzheimer's disease; Biomarker; Choroid; Histopathology; Morphometric analysis; Retina; Vascular biomarkers.

Fig. 1

Illustration of the choroid and its stratified sublayers in a representative control micrograph stained with hematoxylin and eosin on postmortem histopathology.

Fig. 2

Qualitative assessment of the superonasal choroid in representative AD (Top) and control (Bottom) micrographs on light microscopy revealed superonasal choroidal thinning in patients with AD relative controls. Abbreviation: AD, Alzheimer's disease.

Fig. 3

Qualitative assessment of the superotemporal choroid in representative AD (Top) and control (Bottom) micrographs on light microscopy revealed superotemporal choroidal thickening with increased vascularity in patients with AD relative to controls, most pronounced in the macular region. Abbreviation: AD, Alzheimer's disease.

Figure 4

(Top) Illustrates average choroidal thickness comparison between controls (blue) and AD (red) tissue samples for the superonasal and superotemporal regions (∗P < .05). Error bars denote standard deviation. (Bottom) Illustrates comparison of choroidal parameters between AD and control tissue samples within the macular region of the choroid including full choroidal thickness (Full CT); choriocapillaris thickness (CC Th); stromal thickness (Stroma Th) and vessel number for the respective layers (∗P < .05). Abbreviation: AD, Alzheimer's disease.

Fig. 5

Illustrates comparison of choroidal parameters between AD and control tissue samples within the macular region of the choroid including total choroidal area (TCA); total choriocapillaris area (TCCA); total stroma area (TSA); choriocapillaris luminal area (CC LA); stroma luminal area (SLA) (∗P < .05). Abbreviation: AD, Alzheimer's disease.

Fig. 6

Correlation testing for choroidal thickness as a function of vessel number for the stroma (Right) and choriocapillaris (Left).