Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Yu, Wei; Zhang, Ru‐Zhi; Tao, Chuanmin; Xu, Ziqian; Chen, Wei; Wang, Chunhua; Song, Li; Zheng, Jie; Gao, Fabao

doi:10.3348/kjr.2018.19.3.498

Cited by 21 publications

(16 citation statements)

References 30 publications

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“…Finally, animal models have shown that hypertension causes blood-brain barrier disruption [25] and influences Aβ linked-gene expression in the hippocampus [26]. As said, it is not clear whether hypertension is directly involved in the genesis of AD or whether the alterations which it induces constitute a substrate for AD genesis and/or development [24].…”

Section: Role Of Cardiovascular Risk Factors Inmentioning

confidence: 99%

Alzheimer’s Disease and Cardiovascular Disease: A Particular Association

Tini

Scagliola

Monacelli

et al. 2020

Cardiology Research and Practice

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Background and aim. During ageing, the prevalence of dementia, and especially of Alzheimer’s disease (AD) and cardiovascular disease (CVD), increases. The aim of this review is to investigate the relationship between AD and CVD and its risk factors, with a view to explain the underlying mechanisms of this association. Methods. This review is based on the material obtained via MEDLINE (PubMed), EMBASE, and Clinical Trials databases, from January 1980 until May 2019. The search term used was “Alzheimer’s disease,” combined with “cardiovascular disease,” “hypertension,” “dyslipidaemia,” “diabetes mellitus,” “atrial fibrillation,” “coronary artery disease,” “heart valve disease,” and “heart failure.” Out of the 1,328 papers initially retrieved, 431 duplicates and 216 records in languages other than English were removed. Among the 681 remaining studies, 98 were included in our research material on the basis of the following inclusion criteria: (a) the community-based studies; (b) using standardized diagnostic criteria; (c) reporting raw prevalence data; (d) with separate reported data for sex and age classes. Results. While AD and CVD alone may be considered deleterious to health, the study of their combination constitutes a clinical challenge. Further research will help to clarify the real impact of vascular factors on these diseases. It may be hypothesized that there are various mechanisms underlying the association between AD and CVD, the main ones being hypoperfusion and emboli, atherosclerosis, and the fact that, in both the heart and brain of AD patients, amyloid deposits may be present, thus causing damage to these organs. Conclusions. AD and CVD are frequently associated. Further studies are needed in order to understand the effect of CVD and its risk factors on AD in order to better comprehend the effects of subclinical and clinical CVD on the brain. Finally, we need to clarify the impact of the underlying hypothesized mechanisms of this association and to investigate gender issues.

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Section: Role Of Cardiovascular Risk Factors Inmentioning

confidence: 99%

Alzheimer’s Disease and Cardiovascular Disease: A Particular Association

Tini

Scagliola

Monacelli

et al. 2020

Cardiology Research and Practice

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show abstract

“…The animal models of AD driven by Aβ also showed microvascular morphological changes (Iadecola, 2010 ). Vascular risk factors, such as hypertension and diabetes may induce blood-brain barrier and neurovascular unit injury, thus causing chronic cerebral hypoperfusion to adversely affect the neuronal homeostasis and eventually lead to neuronal cell death (Goldwaser et al, 2016 ; Wang et al, 2018 ; Liesz, 2019 ). While individual vascular risk factors could specifically or primarily affect neurovascular unit to varying degrees, their aggregation in clusters may have a broader impact on the cerebrovascular system, including micro-vessels and macro-vessels.…”

Section: Discussionmentioning

confidence: 99%

Aggregation of Vascular Risk Factors Modulates the Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment Patients

Zhuang

Wang

et al. 2020

Front. Aging Neurosci.

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Background: Several vascular risk factors, including hypertension, diabetes, body mass index, and smoking status are found to be associated with cognitive decline and the risk of Alzheimer's disease (AD). We aimed to investigate whether an aggregation of vascular risk factors modulates the amplitude of low-frequency fluctuation (ALFF) in patients with mild cognitive impairment (MCI).Methods: Forty-three MCI patients and twenty-nine healthy controls (HCs) underwent resting-state functional MRI scans, and spontaneous brain activity was measured by the ALFF technique. The vascular risk profile was represented with the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score, and each group was further divided into high and low risk subgroups. Two-way ANOVA was performed to explore the main effects of diagnosis and vascular risk and their interaction on ALFF.Results: The main effect of diagnosis on ALFF was found in left middle temporal gyrus (LMTG) and left superior parietal gyrus (LSPG), and the main effect of risk on ALFF was detected in left fusiform gyrus (LFFG), left precuneus (LPCUN), and left cerebellum posterior lobe (LCPL). Patients with MCI exhibited increased ALFF in the LMTG and LSPG than HCs, and participants with high vascular risk showed increased ALFF in the LFFG and LCPL, while decreased ALFF in the LPCUN. An interaction between diagnosis (MCI vs. HC) and FHS-CVD risk (high vs. low) regarding ALFF was observed in the left hippocampus (LHIP). HCs with high vascular risk showed significantly increased ALFF in the LHIP than those with low vascular risk, while MCI patients with high vascular risk showed decreased ALFF in the LHIP than HCs with high vascular risk. Interestingly, the mean ALFF of LHIP positively correlated with word recall test in HCs with high vascular risk (rho = 0.630, P = 0.016), while negatively correlated with the same test in MCI patients with high vascular risk (rho = −0.607, P = 0.001).Conclusions: This study provides preliminary evidence highlighting that the aggregation of vascular risk factors modulates the spontaneous brain activity in MCI patients, and this may serve as a potential imaging mechanism underlying vascular contribution to AD.

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“…We expected increased astrocytosis particularly in the white matter regions of Wt-AngII and Tg-AngII, accompanied by executive dysfunction, as both white matter and executive function are particularly vulnerable to hypertension (Raz et al, 2003;Vicario et al, 2005;Li et al, 2016). As both hypertension and high levels of amyloid activate both astrocytes and microglia (Vitaioli et al, 2004;Tomassoni et al, 2010;Prokop et al, 2013;Dunn and Nelson, 2014;Shen et al, 2015;von Bernhardi et al, 2015;Frost and Li, 2017;Wang et al, 2018), we expected the greatest amount of glial activity in the comorbid Tg-AngII rats.…”

Section: Introductionmentioning

confidence: 96%

“…These changes are also observed in patients with hypertension (Raz et al, 2003;Vicario et al, 2005;Li et al, 2016). Hypertension disrupts astrocytic polarity (Yamagata et al, 1997;Vitaioli et al, 2004;Tomassoni et al, 2010;Wang et al, 2018), which may be an initiating factor in the development of leukoaraiosis (Huang et al, 2018). Thus, an experimental model that captures the effects of hypertension on white matter astrocytes will be crucial to investigating possible causal relationships between hypertension and AD.…”

Section: Introductionmentioning

confidence: 97%

Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

Levit

Cheng

Hough

et al. 2020

Front. Aging Neurosci.

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Hypertension is recognized as a risk factor for Alzheimer disease, but the causal link remains undetermined. Although astrocytes and microglia play an important role in maintaining the neurovascular unit, astrocytes and microglia have been understudied in comorbid models of hypertension and Alzheimer disease. In this study, male transgenic Fischer 344 rats (TgAPP21) overexpressing a pathogenic human amyloid precursor protein received 8 weeks of Angiotensin II infusion to increase blood pressure, and the rats were evaluated for astrocytosis, microgliosis, and cognitive function. A linear relationship between astrocytosis and blood pressure was observed in the corpus callosum and cingulum of wildtype rats, with hypertensive wildtype rats matching the elevated baseline astrocytosis seen in normotensive transgenic rats. In contrast, hypertensive transgenic rats did not demonstrate a further increase of astrocytosis, suggesting a deficient response. Angiotensin II infusion did not affect activation of microglia, which were elevated in the white matter and hippocampus of transgenic rats. Angiotensin II infusion did impair both wildtype and transgenic rats' executive functions in the Morris Water Maze. These results present important implications for the interaction between hypertension and pathogenic human amyloid precursor protein expression, as Angiotensin II infusion produced cognitive impairments in both genotypes, but transgenic rats were additionally impaired in developing a normal astrocytic response to elevated blood pressure.

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Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Cited by 21 publications

References 30 publications

Alzheimer’s Disease and Cardiovascular Disease: A Particular Association

Alzheimer’s Disease and Cardiovascular Disease: A Particular Association

Aggregation of Vascular Risk Factors Modulates the Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment Patients

Hypertension and Pathogenic hAPP Independently Induce White Matter Astrocytosis and Cognitive Impairment in the Rat

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