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. 2021 Mar 4;13(1):e12162.
doi: 10.1002/dad2.12162. eCollection 2021.

Abnormal retinal capillary blood flow in autosomal dominant Alzheimer's disease

Maxwell B Singer  1 , John M Ringman  2 , Zhongdi Chu  3 , Xiao Zhou  3 , Xuejuan Jiang  1 , Anoush Shahidzadeh  1 , Ruikang K Wang  3   4 , Amir H Kashani  1   2   5   6
Affiliations

Abnormal retinal capillary blood flow in autosomal dominant Alzheimer's disease

Maxwell B Singer et al. Alzheimers Dement (Amst). .

Abstract

Introduction: This study characterizes retinal capillary blood flow in subjects with autosomal dominant Alzheimer's disease (ADAD)-causing mutations.

Methods: Carriers of PSEN1 or APP mutations were prospectively recruited and split into early-stage (ES) and late-stage (LS) groups. Controls were normal subjects and non-carriers from the at-risk group. Capillary blood flow was quantified using an optical coherence tomography angiography-based measure of erythrocyte flux through capillary segments. Statistical analyses were adjusted for correlation between two eyes of the same subject.

Results: ES carriers had significantly greater capillary blood flow than controls and LS carriers. ES and LS carriers had significantly greater capillary blood flow heterogeneity than controls. There was no difference between capillary blood flow of LS carriers and controls.

Discussion: ES ADAD carriers demonstrate increased retinal capillary blood flow and flow heterogeneity compared to controls. These findings support the hypothesis that increased perfusion is a pathophysiologic feature of presymptomatic stages of ADAD.

Keywords: Latino; autosomal dominant Alzheimer's disease; biomarkers; capillary blood flow; optical coherence tomography angiography; retina.

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Conflict of interest statement

John M. Ringman is a DMC member of Renew Group Private Limited and a consultant for InnoSense. Carl Zeiss Meditec has provided grant funding, equipment, and financial support to Amir H Kashani. Ruikang K. Wang holds patents with Carl Zeiss Meditec and Kowa Inc and is a consultant for Carl Zeiss Meditec and Insight Phototonic Solutions.

Figures

FIGURE 1
FIGURE 1
Segmented en face superficial retinal layer (SRL) 3 × 3 mm optical coherence tomography angiography (OCTA) scan centered around the fovea of a control subject. A, Original image of retinal perfusion. B, Image after exclusion of large vessels in yellow and foveal avascular zone (FAZ) in red. C, Skeletonized image of retinal perfusion after exclusion of large vessels in yellow and FAZ in red. D, Pseudo‐colored image of OCTA flux, representing capillary blood flow, with warmer colors corresponding to higher flow
FIGURE 2
FIGURE 2
Segmented en face pseudo‐colored images representing magnitude of capillary flow, in early‐stage (ES) carrier on left, late‐stage (LS) carrier in middle, and control on right. Colder colors correspond to lower flow and warmer colors correspond to higher flow. Flow appears qualitatively greatest in ES carrier
FIGURE 3
FIGURE 3
Histogram distributions of capillary flow values (flux) from all the pixels in an optical coherence tomography angiography scan from a representative control subject and early‐stage carrier (A), and a representative control subject and late‐stage carrier (B). Flow heterogeneity, that is, standard deviation of all pixel flow values, is greater in both the early and late stage carriers than the control subject
FIGURE 4
FIGURE 4
Capillary blood flow and flow heterogeneity among early‐stage (ES) carriers, late‐stage (LS) carriers, and controls. Capillary blood flow is significantly greater in ES carriers than either LS carriers or controls (A), capillary blood flow heterogeneity is significantly greater in ES carriers and LS carriers than in controls (B), capillary density is not significantly different among the three groups in the cohort (C), and vessel caliber is not significantly different among the three groups in the cohort (D). Error bars indicate standard error
See this image and copyright information in PMC

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