2019
DOI: 10.1111/bpa.12759
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Cerebrovascular miRNAs correlate with the clearance of Aβ through perivascular route in younger 3xTg‐AD mice

Abstract: The “two‐hit vascular hypothesis for Alzheimer's disease (AD)” and amyloid‐β (Aβ) oligomer hypothesis suggest that impaired soluble Aβ oligomers clearance through the cerebral vasculature may be an initial step of the AD process. Soluble Aβ oligomers are driven into perivascular spaces from the brain parenchyma and toward peripheral blood flow. The underlying vascular‐based mechanism, however, has not been defined. Given that microRNAs (miRNAs), emerging as novel modulators, are involved in numerous physiologi… Show more

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Cited by 12 publications
(10 citation statements)
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“…Like human AD, the 3xTg-AD mouse exhibits Aβ and tau pathologies with advancing age, coinciding with behavioral deficits (See [ 39 ]). Furthermore, emerging evidence, as seen with molecular biology [ 17 , 40 , 41 ] and cerebrovascular function [ 21 , 42 , 43 ], points to early development of dysregulated cerebral blood flow, vascular permeability, and angiogenesis in the 3xTg-AD mouse model. Thus, the current study focused on a remaining knowledge gap: the structural remodeling of the pial arteries and microcirculation that precedes and/or accompanies AD pathology.…”
Section: Discussionmentioning
confidence: 99%
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“…Like human AD, the 3xTg-AD mouse exhibits Aβ and tau pathologies with advancing age, coinciding with behavioral deficits (See [ 39 ]). Furthermore, emerging evidence, as seen with molecular biology [ 17 , 40 , 41 ] and cerebrovascular function [ 21 , 42 , 43 ], points to early development of dysregulated cerebral blood flow, vascular permeability, and angiogenesis in the 3xTg-AD mouse model. Thus, the current study focused on a remaining knowledge gap: the structural remodeling of the pial arteries and microcirculation that precedes and/or accompanies AD pathology.…”
Section: Discussionmentioning
confidence: 99%
“…Do et al [ 40 ] confirmed the early age (6 months) reductions in cerebrovascular volume prior to pathological alterations. Pericyte coverage in 3xTg-AD mice exhibited a U-shaped function, with early increased coverage at 6 months, followed by a dramatic decline at 9 months, and then an even larger increase by 12 months of age [ 17 ]. This dynamic temporal change in pericyte coverage is intriguing, as it may mirror the changes in the cortical vessel length and decrements in MCA vessel features, as we report ( Figure 3 , Figure 6 and Figure 7 ).…”
Section: Discussionmentioning
confidence: 99%
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“…Such shifts in energy homeostasis would leave individuals with an inability to compensate for the impact of accumulating environmental insults [ 111 ]. Similarly, it has been suggested that the build-up of soluble Aβ oligomers might act as an initial step [ 35 ], that can render individuals vulnerable to subsequent insults that conceivably, occur in the context of slowly unfolding time-dependent genetic programs.…”
Section: Main Textmentioning
confidence: 99%
“…2 Current research has revealed that miRNAs in brain microvessels may promote a highly activated endothelial phenotype, thus promoting elimination of Ab oligomers through perivascular drainage and interfering in the progression of AD. 6 Moreover, transcription factor signal transducer and activator of transcription 3 (STAT3) is activated in reactive astrocytes in several murine and primate models of AD, 7 although inhibition of the STAT3 pathway can prevent astrocyte reactivity and affect the progression of AD.…”
Section: Introductionmentioning
confidence: 99%