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Imagej colocalization analysis5/17/2023 APOE4 also exhibits Aβ-dependent and -independent effects on the cerebrovasculature by reducing cerebral blood flow and increasing the permeability of the blood–brain barrier (BBB). APOE is required for the development of CAA and is a key contributor to fibrillar parenchymal plaque formation. Additionally, APOE is a major constituent in both CAA and plaques. This impaired clearance promotes a self-reinforcing cycle that further deposits Aβ along vessels and in the parenchyma to worsen AD and CAA. Apolipoprotein E (APOE) plays a critical role in lipid transport, although the ε4 allele of the APOE gene is detrimental for both CAA and AD by pathogenically enhancing Aβ aggregation and impairing Aβ clearance. In addition to increasing the risks of intracerebral hemorrhages, vascular Aβ toxicity compromises the neurovascular unit by rendering vascular cells irresponsive to physiological events and impairing perivascular drainage, all of which may exacerbate the progression of AD.ĭespite different mechanisms by which CAA and AD exacerbate Aβ-mediated pathology, CAA and AD share a significant genetic risk factor that increases the prevalence and severity of both diseases. The clinical manifestations, however, are disparate: hyper-phosphorylated aggregated forms of tau are linked with cortical atrophy that strongly correlates with cognitive performance in AD, whereas CAA-associated bleeds and ischemia give rise to vessel dysfunction that accelerates cognitive impairment in AD and non-AD cases. Aβ deposits in the cerebrovasculature as CAA and as neuritic plaques in AD, although CAA co-occurs in 85–95% of AD postmortem brains. For example, the earliest detectable pathological marker of both neurodegenerative diseases includes the accumulation of amyloid-β (Aβ). The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Ĭerebral amyloid angiopathy (CAA) and Alzheimer Disease (AD) are clinically distinct but share overlapping molecular and genetic features. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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