Inflammatory factors are elevated in brain microvessels in Alzheimer's disease

Grammas, Paula; Ovase, Roma

doi:10.1016/s0197-4580(01)00276-7

Cited by 260 publications

(184 citation statements)

References 45 publications

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“…However, due to their non-specific nature, these cytokines can simultaneously damage surrounding healthy tissue [133] via ''by-stander'' injury. Thus, the chronic increase in pro-inflammatory cytokines in the AD brain [134,135] could induce sustained inflammatory-toxicity, causing neuronal dysfunction and ultimately the deterioration observed in AD progression. Furthermore, as noted above, cytokines can also influence AD-related pathology, including Ab and tau [67,79,136,137].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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Neuroinflammatory processes are a central feature of Alzheimer's disease (AD) in which microglia are over-activated, resulting in the increased production of proinflammatory cytokines. Moreover, deficiencies in the antiinflammatory system may also contribute to neuroinflammation. Recently, advanced methods for the analysis of genetic polymorphisms have further supported the relationship between neuroinflammatory factors and AD risk because a series of polymorphisms in inflammation-related genes have been shown to be associated with AD. In this review, we summarize the polymorphisms of both pro-and anti-inflammatory cytokines related to AD, primarily interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha, IL-4, IL-10, and transforming growth factor beta, as well as their functional activity in AD pathology. Exploration of the relationship between inflammatory cytokine polymorphisms and AD risk may facilitate our understanding of AD pathogenesis and contribute to improved treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

2016

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“…For example, anemia is thought to be a key mediator of cognitive impairment in people with ESRD (22,23) and more recently has been associated with cognitive impairment in elderly individuals without known kidney disease (24). Inflammatory mechanisms have been implicated in the pathogenesis of vas- (25) and have been prospectively associated with cognitive decline (12). Serum lipid levels have also been linked with cognitive impairment (26).…”

Section: Discussionmentioning

confidence: 99%

Chronic Kidney Disease and Cognitive Impairment in the Elderly

Kurella¹,

Chertow²,

Fried³

et al. 2005

Journal of the American Society of Nephrology

410

360

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T he prevalence of cognitive impairment and dementia in ESRD is more than double that of the general population (1-3). However, the reasons for this high rate remain uncertain. Specifically, it is not known whether cognitive impairment is mediated by the direct effects of uremia, per se, or is attributable to a high prevalence of predisposing risk factors among individuals with ESRD and side effects of the hemodialysis treatment. Recent studies suggest that chronic kidney disease (CKD) may also be a risk factor for cognitive impairment (4 -6). Many of the factors that have been proposed as mediators of cognitive impairment in ESRD, such as anemia and inflammation, may be present in individuals with earlier stages of CKD (7,8).CKD has been associated with an increased risk for dementia in elderly individuals (4) and with poorer performance on tests of global cognitive function, executive function, language, and memory (5,6). However, previous studies were conducted in mostly white populations and did not explore several hypothesized mediators of impairment, such as anemia and inflammation. Moreover, no studies have examined the association between CKD and performance on serial cognitive function tests, and only one study stratified analyses by the severity of CKD (6). The goals of this study were to determine the strength of the association between CKD and cognitive function in a biracial cohort of community-dwelling elderly and to explore potential mediators of cognitive impairment and whether these extinguish or otherwise modify the association between CKD and cognitive impairment. We hypothesized that CKD would be associated with cognitive impairment in cross-sectional and longitudinal analyses and that the association would be "dose (severity)-dependent" and independent of established risk factors for cognitive impairment, such as age, low educational attainment, diabetes, hypertension, and other cardiovascular disease risk factors.

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“…A related feature of CAA pathology is degeneration of cellular components of the vessel wall and chronic inflammation (Vinters, 1987;Frackowiak et al, 1994;Anders et al, 1997;Grammas and Ovase, 2001;Van Nostrand et al, 2002;Eng et al, 2004;Oh et al, 2004). Characterization of microvessels isolated from AD patients has shown a significant increase in the release of the proinflammatory cytokines interleukin-1␤ (IL-1␤), IL-6, and tumor necrosis factor-␣ compared with control microvessels (Grammas and Ovase, 2001).…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of Cerebral Amyloid Angiopathy-Associated Microhemorrhage in Amyloid Precursor Protein Transgenic Mice by Immunotherapy Is Dependent on Antibody Recognition of Deposited Forms of Amyloid β

Racke¹,

Boone²,

Hepburn³

et al. 2005

J. Neurosci.

294

238

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Passive immunization with an antibody directed against the N terminus of amyloid ␤ (A␤) has recently been reported to exacerbate cerebral amyloid angiopathy (CAA)-related microhemorrhage in a transgenic animal model. Although the mechanism responsible for the deleterious interaction is unclear, a direct binding event may be required. We characterized the binding properties of several monoclonal anti-A␤ antibodies to deposited A␤ in brain parenchyma and CAA. Biochemical analyses demonstrated that the 3D6 and 10D5, two N-terminally directed antibodies, bound with high affinity to deposited forms of A␤, whereas 266, a central domain antibody, lacked affinity for deposited A␤. To determine whether 266 or 3D6 would exacerbate CAA-associated microhemorrhage, we treated aged PDAPP mice with either antibody for 6 weeks. We observed an increase in both the incidence and severity of CAA-associated microhemorrhage when PDAPP transgenic mice were treated with the N-terminally directed 3D6 antibody, whereas mice treated with 266 were unaffected. These results may have important implications for future immune-based therapeutic strategies for Alzheimer's disease.

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Inflammatory factors are elevated in brain microvessels in Alzheimer's disease

Cited by 260 publications

References 45 publications

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Inflammatory Cytokines and Alzheimer’s Disease: A Review from the Perspective of Genetic Polymorphisms

Chronic Kidney Disease and Cognitive Impairment in the Elderly

Exacerbation of Cerebral Amyloid Angiopathy-Associated Microhemorrhage in Amyloid Precursor Protein Transgenic Mice by Immunotherapy Is Dependent on Antibody Recognition of Deposited Forms of Amyloid β

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