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. 2024 Jun;20(6):4185-4198.
doi: 10.1002/alz.13871. Epub 2024 May 15.

Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease

William Robert Kwapong  1 , Fei Tang  2 , Peng Liu  3 , Ziyi Zhang  1 , Le Cao  1 , Zijuan Feng  1 , Shiyun Yang  1 , Yang Shu  2 , Heng Xu  2 , Ying Lu  2 , Xinjun Zhao  2 , Baochen Chong  2 , Bo Wu  1 , Ming Liu  1 , Peng Lei  1   2 , Shuting Zhang  1
Affiliations

Choriocapillaris reduction accurately discriminates against early-onset Alzheimer's disease

William Robert Kwapong et al. Alzheimers Dement. 2024 Jun.

Abstract

Introduction: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers.

Methods: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts.

Results: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aβ)42, Aβ42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement.

Discussion: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aβ and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD.

Highlights: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

Keywords: amyloid beta; choriocapillaris; early‐onset dementia; retinal microvasculature; tau.

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Conflict of interest statement

The sponsor had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the study data. The corresponding author had final responsibility for the decision to submit the manuscript for publication. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Flowchart of study design and patient inclusion. APOE, apolipoprotein E; EOAD, early‐onset Alzheimer's disease; MRI, magnetic resonance imaging; SD‐OCTA, spectral domain optical coherence tomography angiography; SS‐OCTA, swept‐source optical coherence tomography angiography.
FIGURE 2
FIGURE 2
The choriocapillaris and serum biomarkers in SS‐OCTA cohort. A, Comparison of SS‐OCTA parameters between the control and EOAD groups (data source: Table 1); (B) ROC analysis of SS‐OCTA parameters (data source: Table 1); (C) comparison of serum biomarkers between the control and EOAD groups (data source: Table 1); (D) ROC analysis of SS‐OCTA parameters (data source: Table 1); (E) linear correlation between choriocapillaris and serum biomarkers in EOAD (data source: Table 3); (F) linear correlation between choriocapillaris and parietal lobe volume in EOAD (data source: Table S3). DCP, deep capillary plexus; EOAD, early‐onset Alzheimer's disease; ICP, intermediate capillary plexus; ROC, receiver operating characteristic; SS‐OCTA, swept‐source optical coherence tomography angiography; SVP, superficial vascular plexus.
FIGURE 3
FIGURE 3
The choriocapillaris and serum biomarkers in SD‐OCTA cohort. A, Comparison of SD‐OCTA parameters between the control and EOAD groups (data source: Table 2); (B) ROC analysis of SD‐OCTA parameters (data source: Table 2); (C) comparison of serum biomarkers between the control and EOAD groups (data source: Table 2); (D) ROC analysis of SD‐OCTA parameters (data source: Table 2). DVC, deep vascular complex; EOAD, early‐onset Alzheimer's disease; ICP, intermediate capillary plexus; ROC, receiver operating characteristic; SD‐OCTA, spectral domain optical coherence tomography angiography; SVC, superficial vascular complex.
FIGURE 4
FIGURE 4
The choriocapillaris and serum biomarkers according to APOE in SS‐OCTA cohort. A, Comparison of serum biomarkers according to APOE in EOAD (data source: Table 4); (B) comparison of SS‐OCTA parameters according to APOE in EOAD (data source: Table 4). APOE, apolipoprotein E; DCP, deep capillary plexus; ICP, intermediate capillary plexus; SS‐OCTA, swept‐source optical coherence tomography angiography; SVP, superficial vascular plexus.
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