Mapping of microvascular architecture in the brain of an Alzheimer's disease mouse model using MRI.

Suk‐Ki Chang,Chang‐Woo Ryu,Dongkyu Lee,Geon‐Ho Jahng,Hak Young Rhee,Jong Kil Lee,Chang Hyun Yoo,Hyungjoon Cho,Seokha Jin,Jeongyeong Kim

doi:10.1002/nbm.4481

Abstract

Increasing evidence suggests that alterations in cerebral microvasculature play a critical role in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture of AD transgenic (Tg) mice and compare it with that of non-Tg mice using brain microvascular indices obtained by MRI. Seven non-Tg mice and 10 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after the injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculating ΔR2* and ΔR2, the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density, mean vessel-weighted image (MvWI) and blood volume fraction (BVf) were mapped. Voxel-based analyses and region of interest (ROI)-based analyses were performed to compare the indices of the non-Tg and Tg groups. Voxel comparisons showed that BVf, mVD, VSI and MvWI were greater in the Tg group than in the non-Tg group. Additionally, the ROI-based analysis showed that ΔR2*, BVf, mVD, MvWI and VSI increased in several brain regions of the Tg group compared with those in the non-Tg group. VSI and mVD increased in Tg mice; these findings indicated microvascular disruption in the brain that could be related to damage to the neurovascular unit in AD caused by cerebral amyloid angiopathy.

Highlights

Alzheimer’s disease (AD) and its risk factors Alzheimer’s disease (AD) is defined as a neurodegenerative disorder characterized by a gradual decline in memory and other cognitive functions and is neuropathologically associated with the accumulation of extracellular amyloid-β peptide (Aβ), intracellular neurofibrillary tangles, and hyper-phosphorylated microtubule-associated protein tau [1]
The mean vessel diameter (mVD), vessel size index (VSI), and mean vessel-weighted image (MvWI) were greater in the Tg group than in the non-Tg group
Some theories suggest that cerebrovascular dysfunction precedes cognitive decline, and the onset of neurodegenerative changes in AD indicate that cerebral hypoperfusion impairs the clearance of Aß from the brain, which is normally performed by the cells in the neurovascular unit

Summary

Introduction

Alzheimer’s disease (AD) and its risk factors Alzheimer’s disease (AD) is defined as a neurodegenerative disorder characterized by a gradual decline in memory and other cognitive functions and is neuropathologically associated with the accumulation of extracellular amyloid-β peptide (Aβ), intracellular neurofibrillary tangles, and hyper-phosphorylated microtubule-associated protein tau [1]. The microvascular structures in AD revealed by autopsy demonstrate decreased smooth muscle actin, resulting in an increase in wall thickness of the cerebral artery caused by accumulation of Aβ and/or the protein tau [2]. CAA causes a decrease in brain perfusion in AD due to compromised interstitial fluid drainage, resulting from the destruction of the perivascular spaces due to the microvascular accumulations of amyloid-beta. Damage to the cerebral microvasculature is caused by abnormalities of the cerebrovascular walls, including smooth muscle cells, which show fibrinoid necrosis, as well as weakness of the vessel wall [7] and capillary occlusion,[8]. Genetic risk factors for AD are associated with neurotoxicity of Aβ associated with CAA [10]

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