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[Preprint]. 2024 Feb 29:2024.02.27.580733. [Version 1] doi: 10.1101/2024.02.27.580733

Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance

Oana M Dumitrascu, Jonah Doustar, Dieu-Trang Fuchs, Yosef Koronyo, Dale S Sherman, Michelle Shizu Miller, Kenneth O Johnson, Roxana O Carare, Steven R Verdooner, Patrick D Lyden, Julie A Schneider, Keith L Black, Maya Koronyo-Hamaoui
PMCID: PMC10925252  PMID: 38464292

Abstract

Introduction

The vascular contribution to Alzheimer’s disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition.

Methods

Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures.

Results

Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count.

Discussion

Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD.

Highlights:

  • Retinal peri-arteriolar region exhibits more amyloid compared with peri-venular regions.

  • Secondary retinal vascular branches have significantly higher perivascular amyloid burden in subjects with impaired cognition, consistent across sexes.

  • Cognitively impaired individuals have significantly greater retinal peri-venular amyloid deposits in the distal small branches, that correlate with CDR and hippocampal volumes.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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