scholarly journals Hypertension and Alzheimer’s disease: indirect effects through circle of Willis atherosclerosis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Graham M L Eglit ◽  
Alexandra J Weigand ◽  
Daniel A Nation ◽  
Mark W Bondi ◽  
Katherine J Bangen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Indirect Effects ◽  
Arterial Wall ◽  
Circle Of Willis ◽  
Cerebral Hypoperfusion ◽  
Vascular Risk ◽  
Neuritic Plaques ◽  
Continuous Measures

Abstract Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer’s disease, but mechanisms underlying this relationship are unclear. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer’s disease. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer’s disease neuropathology, we analysed post-mortem neuropathological data on 2198 decedents from the National Alzheimer’s Coordinating Center database [mean (standard deviation) age at last visit 80.51 (1.95) and 47.1% female] using joint simultaneous (i.e. mediation) modelling. Within the overall sample and among Alzheimer’s dementia decedents, hypertension was indirectly associated with increased neuritic plaques and neurofibrillary tangles through its association with circle of Willis atherosclerosis. Similar indirect effects were observed for continuous measures of systolic and diastolic blood pressure. These results suggest that hypertension may promote Alzheimer’s disease pathology indirectly through intracranial atherosclerosis by limiting cerebral blood flow and/or dampening perivascular clearance. Circle of Willis atherosclerosis may be an important point of convergence between vascular risk factors, cerebrovascular changes and Alzheimer’s disease neuropathology.

Circle of Willis atherosclerosis: association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles

2006 ◽  
Vol 113 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Thomas G. Beach ◽  
Jeffrey R. Wilson ◽  
Lucia I. Sue ◽  
Amanda Newell ◽  
Marissa Poston ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Circle Of Willis ◽  
Neuritic Plaques

scholarly journals RCAN1 Inhibits BACE2 Turnover by Attenuating Proteasome-Mediated BACE2 Degradation

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Kaixin Qiu ◽  
Shuai Wang ◽  
Xin Wang ◽  
Fengting Wang ◽  
Yili Wu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein A ◽  
Potential Mechanism ◽  
Neuritic Plaques ◽  
Protein Levels ◽  
Bace1 Expression ◽  
Main Component

Amyloid-β protein (Aβ) is the main component of neuritic plaques, the pathological hallmark of Alzheimer’s disease (AD). β-site APP cleaving enzyme 1 (BACE1) is a major β-secretase contributing to Aβ generation. β-site APP cleaving enzyme 2 (BACE2), the homolog of BACE1, is not only a θ-secretase but also a conditional β-secretase. Previous studies showed that regulator of calcineurin 1 (RCAN1) is markedly increased by AD and promotes BACE1 expression. However, the role of RCAN1 in BACE2 regulation remains elusive. Here, we showed that RCAN1 increases BACE2 protein levels. Moreover, RCAN1 inhibits the turnover of BACE2 protein. Furthermore, RCAN1 attenuates proteasome-mediated BACE2 degradation, but not lysosome-mediated BACE2 degradation. Taken together, our work indicates that RCAN1 inhibits BACE2 turnover by attenuating proteasome-mediated BACE2 degradation. It advances our understanding of BACE2 regulation and provides a potential mechanism of BACE2 dysregulation in AD.

Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress

2012 ◽  
Vol 385 (10) ◽  
pp. 953-959 ◽  
Author(s):  
Hyun Ah Kim ◽  
Alyson A. Miller ◽  
Grant R. Drummond ◽  
Amanda G. Thrift ◽  
Thiruma V. Arumugam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Cerebral Hypoperfusion ◽  
And Oxidative Stress

scholarly journals Role of Vascular Risk Factors and Vascular Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 77 (1) ◽  
pp. 82-102 ◽  
Author(s):  
Dara L. Dickstein ◽  
Jessica Walsh ◽  
Hannah Brautigam ◽  
Steven D. Stockton ◽  
Samuel Gandy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dysfunction ◽  
Vascular Risk Factors ◽  
Vascular Risk

scholarly journals Lessons From Mixed Dementia

1997 ◽  
Vol 9 (3) ◽  
pp. 245-249 ◽  
Author(s):  
Kenneth Rockwood
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Vascular Risk Factors ◽  
Vascular Injuries ◽  
Vascular Risk ◽  
Mixed Dementia ◽  
Dementia Syndrome

With reconsideration of the role of vascular risk factors for Alzheimer's disease (AD; Gorelick et al., 1996), and with a recent Consortium to Establish a Registry for Alzheimer's Disease (CERAD) report that pure vascular dementia may be more difficult to find than has been widely assumed (Hulette et al., 1997), it is appropriate to reevaluate our understanding of so-called mixed dementia, or the dementia syndrome that arises from the combination of AD and ischemic vascular injuries. Such a reevaluation leads to potentially important lessons, an outline of which is presented here.

scholarly journals Oxidative Stress and Hypoxia Contribute to Alzheimer's Disease Pathogenesis: Two Sides of the Same Coin

2009 ◽  
Vol 9 ◽  
pp. 781-791 ◽  
Author(s):  
Michela Guglielmotto ◽  
Elena Tamagno ◽  
Oliviero Danni
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Hypoperfusion ◽  
Oxygen Species ◽  
Disease Pathogenesis ◽  
App Processing ◽  
Secretase Activity ◽  
Two Sides

While it is well established that stroke and cerebral hypoperfusion are risk factors for Alzheimer's disease (AD), the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has only been recently established. Here we review the role of the release of reactive oxygen species (ROS) by the mitochondrial electron chain in response to hypoxia, providing evidence that hypoxia fosters the amyloidogenic APP processing through a biphasic mechanism that up-regulates β-secretase activity, which involves an early release of ROS and an activation of HIF-1α.

Epidemiology of Alzheimer’s disease

2011 ◽  
Author(s):  
Chengxuan Qiu ◽  
Laura Fratiglioni
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
Expert Panel ◽  
Current Evidence ◽  
Vascular Risk ◽  
Panel Estimates ◽  
Dementing Disorders

• Alzheimer’s disease is the most frequent type of dementia in elderly people. An expert panel estimates that worldwide more than 24 million people are affected by dementia, most suffering from Alzheimer’s disease• The etiological factors other than old age and genetic susceptibility for Alzheimer’s disease remain to be determined, but current evidence strongly supports the potential role of vascular risk factors and psychosocial factors in the pathogenetic process and clinical manifestation of the dementing disorders...

scholarly journals Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 199
Author(s):  
Donald J. Alcendor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ethnic Minorities ◽  
Ethnic Disparities ◽  
Cerebral Hypoperfusion ◽  
Cerebral Vascular Disease ◽  
Endothelin 1 ◽  
The Impact ◽  
Cerebral Vascular

Alzheimer’s disease (AD) and related dementias disproportionately impact racial and ethnic minorities. The racial and ethnic disparities in AD could be explained by differences in cerebral vascular disease pathology. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide that regulates smooth muscle, endothelial cell, and pericyte contractions that may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, ET-1 may result in neuronal injury contributing to the pathology of AD. Upregulation of the ET-1 system has been observed in African Americans when compared with non-Hispanic Whites. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. Targeting of the ET-1 system as a therapeutic intervention that could impact AD progression also needs further study. Dysregulation of ET-1 in Hispanic/Latino populations largely have been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also needs further investigation. In this review, I examine how AD effects underserved minority populations and how dysregulation of the ET-1 system specifically predisposes ethnic minorities to AD. In addition, I examine the molecular interactions of the ET-1 system and amyloid beta, the role the ET-1 system in neurodegeneration, potential therapeutics for ET-1 dysregulation, and the impact on AD progression.

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