In vivo characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography

Yao Yu; Ning Zhang; Ben Xiang; Ning Ding; Jian Liu; Jiangmei Huang; Min Zhao; Yuqian Zhao; Yi Wang; Zhenhe Ma

doi:10.1117/1.NPh.10.1.015005

16 February 2023 In vivo characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography

Yao Yu, Ning Zhang, Ben Xiang, Ning Ding, Jian Liu, Jiangmei Huang, Min Zhao, Yuqian Zhao, Yi Wang, Zhenhe Ma

Author Affiliations +

Neurophotonics, Vol. 10, Issue 1, 015005 (February 2023). https://doi.org/10.1117/1.NPh.10.1.015005

Abstract

Significance

Antiamyloid β (Aβ) immunotherapy is a promising therapeutic strategy for Alzheimer’s disease (AD) but generates large amounts of soluble Aβ peptides that could overwhelm the clearance pathway, leading to serious side effects. Direct implications of Aβ in glymphatic drainage transport for cerebral vasculature and tissue are not well known. Studies are needed to resolve this issue and pave the way to better monitoring abnormal vascular events that may occur in Aβ-modifying therapies for AD.

Aim

The objective is to characterize the modification of cerebral vasculature and tissue induced by soluble Aβ abundantly present in the glymphatic clearance system.

Approach

Aβ_{1 − 42} peptide was injected intracerebroventricularly and swept-source optical coherence tomography (SS-OCT) was used to monitor the progression of changes in the brain microvascular network and tissue in vivo over 14 days. Parameters reflecting vascular morphology and structure as well as tissue status were quantified and compared before treatment.

Results

Vascular perfusion density, vessel length, and branch density decreased sharply and persistently following peptide administration. In comparison, vascular average diameter and vascular tortuosity were moderately increased at the late stage of monitoring. Endpoint density gradually increased, and the global optical attenuation coefficient value decreased significantly over time.

Conclusions

Aβ burden in the glymphatic system directly contributes to cerebrovascular structural and morphological abnormalities and global brain tissue damage, suggesting severe deleterious properties of soluble cerebrospinal fluid-Aβ. We also show that OCT can be used as an effective tool to monitor cerebrovascular dynamics and tissue property changes in response to therapeutic treatments in drug discovery research.

CC BY: © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Yao Yu, Ning Zhang, Ben Xiang, Ning Ding, Jian Liu, Jiangmei Huang, Min Zhao, Yuqian Zhao, Yi Wang, and Zhenhe Ma "In vivo characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography," Neurophotonics 10(1), 015005 (16 February 2023). https://doi.org/10.1117/1.NPh.10.1.015005

Received: 2 October 2022; Accepted: 20 January 2023; Published: 16 February 2023

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