Alzheimer’s disease and the ‘ABSENT’ hypothesis: mechanism for amyloid β endothelial and neuronal toxicity

Roy, Samir; Rauk, Arvi

doi:10.1016/j.mehy.2004.08.031

Cited by 33 publications

(22 citation statements)

References 125 publications

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“…Furthermore, cerebrovascular disease has been reported to worsen cognitive function in the early stages of AD subjects [70], where levels of oxidative stress are thought to be increased and clinically diagnosed AD patients at postmortem examination have significant lesion formation present in the main artery to brain [71] suggesting that these cardiovascular lesions, which may lead to ischemic conditions associated with VaD are also evident in AD. The recently proposed Amyloid Beta Synergistic Endothelial and Neurotoxicity (ABSENT) hypothesis by Roy and Rauk [7] reinforces that not all hallmarks indicative of AD or VaD can be explained by either form of dementia. Further, they suggest that the effects of Aβ on neuronal and vascular tissue act in synergy thus promoting AD onset and progression, but suggest that Aβ, a source of free radicals, is required to cause these dementias.…”

Section: Link Between Cerebral Ischemia and Vasoconstriction Of Bloodmentioning

confidence: 92%

“…Links have recently been proposed between vascular dysfunction and Aβ where the ratio of Aβ plaques to vascular lesions is suggested to be indicative of the form of dementia from which an individual is suffering [7]. A recent review by Launer and colleagues [8] discussed epidemiological studies focused on VaD and AD and the potential role that vascular factors have in AD.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Bennett

Grant

Aldred

2008

JAD

211

145

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Alzheimer's disease and vascular dementia are the two most common types of dementia with the former being the most predominant. It is evident that oxidative stress, an environment where pro-oxidant species overwhelm antioxidant species, is involved in the pathogenesis of both forms of dementia. An increased level of reactive oxygen species in the vasculature, reduced nitric oxide bioavailability, and endothelial dysfunction leading to vascular disease is associated with vascular dementia. In Alzheimer's disease, an increased amount of amyloid-beta peptide induces elevated reactive oxygen species production thereby causing neuronal cell death and damage. The recent observation that increased atherosclerotic plaque formation is present in the main artery to the brain in Alzheimer's disease, coupled with the association of vascular risk factors with this disease, suggests a link between these two dementias. This review will argue that Alzheimer's disease and vascular dementia are two extremes of one disease, thus assuming a hypothesis where the clinical conditions referred to as dementia are part of a continuum. We propose that the majority of cases share a vascular pathology and that oxidative stress is central to this common pathology.

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Section: Link Between Cerebral Ischemia and Vasoconstriction Of Bloodmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Bennett

Grant

Aldred

2008

JAD

211

145

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“…-amyloid peptides (A ) deposits in neurons are one of the prominent features of AD. Links have recently been proposed between vascular dysfunction and A where the ratio of A plaques to vascular lesions is suggested to be indicative of the form of dementia [3]. The oxidative damage might be involved in cerebrovascular dysfunction especially for the cerebrovascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Flavonoids Protect Cerebrovascular Endothelial Cells through Nrf2 and PI3K from β-Amyloid Peptide-Induced Oxidative Damage

Yu²,

Ding³

et al. 2012

CNR

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β-amyloid peptides (Aβ) induced cerebrovascular dysfunction has been recognized as a vital factor involved in the pathogenesis of neurodegeneration. Genistein, a flavonoid, has antioxidative properties to prevent neurodegeneration induced by β-amyloid peptides. In this study, we were investigating whether genistein could antagonize oxidative damage induced by β-amyloid peptide 25-35 (Aβ25-35) in bEND.3 cells, and also identifying the potential neuroprotective targets of genistein. Vitamin E was used as the positive control. The bEND.3 cells were pre-incubated with/out genistein or vitamin E for 2 h followed by the incubation with 25 μM A 25-35 for another 24 h. The reactive oxygen species (ROS), nitrotyrosine, cell redox state, mRNA or protein expressions of the factors on Nrf2 signaling pathway were measured after Aβ25-35 treatment. The results showed that genistein alleviated the increase of ROS and nitrotyrosine production induced by Aβ25-35, and maintained bEND.3 cell redox state by increasing GSH level and GSH/GSSG. Genistein could reverse the down-regulation of total protein and mRNA expression of NF-E2-related factor 2 (Nrf2), nuclear Nrf2, γ-glutamylcysteine synthetase (γ-GCS), phosphatidylinositol 3-kinase (PI3K) induced by Aβ25-35; while PI3K inhibitor LY294002 could attenuate the activation effects of genistein on Nrf2, especially for the promotion of nuclear translocation. These results suggested that genistein could protect cerebrovascular endothelial cells from Aβ25-35-induced oxidative damage. The potential mechanisms might be associated with the activation of Nrf2 signaling pathway by modulating PI3K activity.

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“…In addition, β-amyloid proteins can also promote excessive production of free radicals in endothelial cells, which are responsible for neuronal cell death. 28 We also acknowledge that our results have several limitations. First of all, our study was not randomized and the effect of treatment on outcome must be cautiously interpreted in the context of an observational study which was not designed to evaluate the impact of prescriptions on prognosis.…”

Section: Discussionmentioning

confidence: 86%

Effects of Antihypertensive Therapy on Cognitive Decline in Alzheimer's Disease

Duron

Rigaud

Dubail

et al. 2009

American Journal of Hypertension

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Alzheimer’s disease and the ‘ABSENT’ hypothesis: mechanism for amyloid β endothelial and neuronal toxicity

Cited by 33 publications

References 125 publications

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Flavonoids Protect Cerebrovascular Endothelial Cells through Nrf2 and PI3K from β-Amyloid Peptide-Induced Oxidative Damage

Effects of Antihypertensive Therapy on Cognitive Decline in Alzheimer's Disease

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Alzheimer’s disease and the ‘ABSENT’ hypothesis: mechanism for amyloid β endothelial and neuronal toxicity

Cited by 33 publications

References 125 publications

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Oxidative Stress in Vascular Dementia and Alzheimer's Disease: A Common Pathology

Flavonoids Protect Cerebrovascular Endothelial Cells through Nrf2 and PI3K from &#946;-Amyloid Peptide-Induced Oxidative Damage

Effects of Antihypertensive Therapy on Cognitive Decline in Alzheimer's Disease

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Product

Resources

About

Flavonoids Protect Cerebrovascular Endothelial Cells through Nrf2 and PI3K from β-Amyloid Peptide-Induced Oxidative Damage