Article
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Vascular Heparan Sulfate and Amyloid-β in Alzheimer’s Disease Patients
Version 1
: Received: 8 February 2024 / Approved: 9 February 2024 / Online: 9 February 2024 (10:05:34 CET)
A peer-reviewed article of this Preprint also exists.
McMillan, I.O.; Gearing, M.; Wang, L. Vascular Heparan Sulfate and Amyloid-β in Alzheimer’s Disease Patients. Int. J. Mol. Sci. 2024, 25, 3964. McMillan, I.O.; Gearing, M.; Wang, L. Vascular Heparan Sulfate and Amyloid-β in Alzheimer’s Disease Patients. Int. J. Mol. Sci. 2024, 25, 3964.
Abstract
Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, the latter termed cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) within the cerebrovasculature and its potential associations with CAA, gender, and ApoE4 genotype. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher colocalization of HS with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebral vasculature was detected in AD patients with severe CAA, suggesting a potential role in CAA development. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings shed light on the intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further exploring the underlying mechanisms may present novel therapeutic avenues for AD treatment.
Keywords
Alzheimer’s Disease; heparan sulfate; amyloid-β; cerebral amyloid angiopathy; cerebrovasculature; gender; ApoE; endothelial cell; smooth muscle cell
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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