Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration

Jeon, So Yeon; Byun, Min Soo; Yi, Dahyun; Lee, Jun Ho; Choe, Young Min; Ko, Kang; Sohn, Bo Kyung; Choi, Hyo Jung; Lee, Jun-Young; Lee, Dong Hoon

doi:10.1016/j.neurobiolaging.2018.11.001

Cited by 32 publications

(27 citation statements)

References 59 publications

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“…The finding that the HTN/APOE4+ group had a steeper decline in FDG SUVR than all other groups among cognitively normal older people is novel. Consistent with our finding, previous observational studies showed that the influence of hypertension on cognitive deficits, medial temporal atrophy, subcortical white matter lesions, cortical amyloid deposition, and tau phosphorylation was greater in APOE4 carriers than in APOE4 non-carriers (Peila et al, 2001;De Leeuw et al, 2004;Korf et al, 2004;Den Heijer et al, 2005;Kester et al, 2010;De Frias et al, 2014;Andrews et al, 2015;Oberlin et al, 2015;Jeon et al, 2019). Collectively these data and ours indicate that the impact of hypertension on neuronal damage and synapse loss appears to be exacerbated by the APOE4 allele.…”

Section: Discussionsupporting

confidence: 92%

“…Similarly, compared to APOE4 non-carriers, APOE4 carriers shows a greater amount of amyloid and tau pathologies (Leoni, 2011). More importantly, a recent study using [11C]-Pittsburgh-compound-B-positron emission tomography showed that in APOE4 carriers, hypertension was associated with increased cortical Aβ accumulation (Jeon et al, 2019), which could contribute to brain glucose hypometabolism (Lowe et al, 2014). Therefore, the effect of hypertension on neuronal injury, measured by FDG SUVR, would be expected to be larger for APOE4 carriers.…”

Section: Discussionmentioning

confidence: 99%

“…There is a possibility that the APOE4 allele may interact with other cardiovascular diseases [e.g., hypertension (HTN)] to affect the levels of brain glucose metabolism. In line with this notion, previous observational studies indicated that APOE4 and HTN act synergistically to influence cognitive performance, subcortical white matter integrity, and cortical amyloid accumulation (Peila et al, 2001;De Leeuw et al, 2004;De Frias et al, 2014;Oberlin et al, 2015;Jeon et al, 2019). However, no prior studies have attempted to assess the contributions of the APOE4 and HTN status to longitudinal changes in brain glucose metabolism among older individuals with normal cognition.…”

Section: Introductionmentioning

confidence: 95%

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Influence of Hypertension on Longitudinal Changes in Brain Glucose Metabolism Was Modified by the APOE4 Allele Among Cognitively Normal Older Individuals

Zhou

Chen

et al. 2020

Front. Aging Neurosci.

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Objective: To examine whether the influence of hypertension (HTN) status on longitudinal changes in brain glucose metabolism was modified by the apolipoprotein 4 (APOE4) status among older people with normal cognition. Methods: In this study, we included 217 older individuals with normal cognition from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Participants were divided into the HTN and no HTN groups based on self-reported medical history. Brain glucose metabolism was assessed by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Linear mixed model was fitted to examine the association between the HTN × APOE4 interaction and longitudinal changes in brain glucose metabolism after controlling for several covariates. Results: In the present study, we found that the association between HTN status and longitudinal changes in brain glucose metabolism varied as a function of the APOE4 status, such that the HTN/APOE4+ group showed a steeper decline in FDG SUVR than all other groups (No HTN/APOE4-, HTN/APOE4-, and No HTN/APOE4+). Nevertheless, there was no significant difference in the rate of decline in FDG SUVR among other groups (No HTN/APOE4-, HTN/APOE4-, and No HTN/APOE4+). Conclusion: The APOE4 genotype interacted with hypertension status to affect longitudinal changes in brain glucose metabolism among older individual with normal cognition, such that the HTN/APOE4+ group showed a steeper decline in FDG SUVR than other groups.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Influence of Hypertension on Longitudinal Changes in Brain Glucose Metabolism Was Modified by the APOE4 Allele Among Cognitively Normal Older Individuals

Zhou

Chen

et al. 2020

Front. Aging Neurosci.

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“…Vascular damage, including capillary rarefaction, blood-brain barrier disruption, and consequential neuroinflammation, impairs neurovascular-coupling responses and promotes the genesis of cerebral microhemorrhages [14,15]. It explains many of the biological processes and pathogenesis of AD and this is supported by many epidemiological and experimental studies [14,[16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Zhang

et al. 2020

IJMS

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Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein–protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids’ anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer’s disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.

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“…Examples include a 20-year longitudinal study, which found that cardiovascular risk factors such as hypertension, BMI from midlife to late life also increased the risk of severe white matter lesion in the brain [9]. A recent study also found a correlation between hypertension and reduction in brain reserve [10], and therefore adopting a healthy lifestyle may reduce the chances of hypertension which in turn also delay the onset of AD. Similar trends have been observed in nutrition studies [11].…”

Section: Modifiable Risk Factorsmentioning

confidence: 99%

Application of Big Data and Artificial Intelligence technologies to dementia prevention research: an opportunity for low-and-middle-income countries

Danso

Muñiz‐Terrera

Luz

et al. 2019

Journal of Global Health

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I t is estimated that about 66% of the number of people with dementia globally live in regions within the low-and-middle-income countries (LMIC). The estimates further suggest that about 1 million additional cases are recorded annually in these LMICs, with approximately 60-70% of the dementia cases being due to Alzheimer disease, AD [1]. Despite this high incidence of AD, treatment options are currently limited. This is notwithstanding the fact that numerous clinical trials have taken place, are still on going or planned [2]. However, the rate of failure of clinical trials and predictions based on available results from randomised control trials suggest that an immediate breakthrough to obtaining treatment drugs for AD is unlikely [3].

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Influence of hypertension on brain amyloid deposition and Alzheimer's disease signature neurodegeneration

Cited by 32 publications

References 59 publications

Influence of Hypertension on Longitudinal Changes in Brain Glucose Metabolism Was Modified by the APOE4 Allele Among Cognitively Normal Older Individuals

Influence of Hypertension on Longitudinal Changes in Brain Glucose Metabolism Was Modified by the APOE4 Allele Among Cognitively Normal Older Individuals

A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer’s Disease

Application of Big Data and Artificial Intelligence technologies to dementia prevention research: an opportunity for low-and-middle-income countries

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