Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease

Abstract

Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of innate immunity are involved in several crucial pathogenic events of the underlying pathological cascade in AD, and recent studies have shown that innate immunity is involved in the etiology of late-onset AD. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. Neuropathological and experimental studies indicate that fibrillar amyloid-β (Aβ) can activate the innate immunity-related CD14 and Toll-like receptor signaling pathways of glial cells for pro-inflammatory cytokine production. The production capacity of this pathway is under genetic control and offspring with a parental history of late-onset AD have a higher production capacity for pro-inflammatory cytokines. The activation of microglia by fibrillar Aβ deposits in the early preclinical stages of AD can make the brain susceptible later on for a second immune challenge leading to enhanced production of pro-inflammatory cytokines. An example of a second immune challenge could be systemic inflammation in patients with preclinical AD. Prospective epidemiological studies show that elevated serum levels of acute phase reactants can be considered as a risk factor for AD. Clinical studies suggest that peripheral inflammation increases the risk of dementia, especially in patients with preexistent cognitive impairment, and accelerates further deterioration in demented patients. The view that peripheral inflammation can increase the risk of dementia in older people provides scope for prevention.

Antioxidant and anti-inflammatory properties of selected polyherbal preparations: Oroki herbal, Swedish bitters and Yoyo bitters

“…According to the previous study, both erythrocyte and lysosomal membrane have a similar molecular composition, hence, any agent that could stabilize the red blood cell membrane from hemolysis would provide a good insight into the anti-inflammatory mechanism of action [21]. More so, epidemiological and experimental studies have suggested an association between acute and chronic inflammation and risk of developing numerous pathological disorders [23,24]. Hence, natural compounds from plants that mitigate against inflammation could serve as therapy in the management of inflammation-mediated disorders.…”

Hepatic Expression of Serum Amyloid A1 Is Induced by Traumatic Brain Injury and Modulated by Telmisartan

“…75,76 Systemic inflammation can increase cytokine expression in the brain and initiate amyloid deposition via activation of microglial cells and amyloid-associated proteins. 29,77 We have demonstrated that the expression of SAA1 in the liver after brain injury did not result in the formation of detectable amyloid species. Because SAA1 levels decreased significantly by 3 dpi, presumably persistent accumulation of SAA1 for a longer time period is needed to initiate amyloid formation.…”

The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease

“…Several prospective epidemiological studies have found that increased acute phase mediator serum levels can serve as a risk factor for AD, as detailed in a review article by Eikelenboom et al 78 In addition, other clinical studies compiled in the review have suggested that increased peripheral inflammation is associated with a greater risk of dementia, mainly in patients with pre-existing cognitive impairments, and accelerates subsequent deterioration in patients with dementia. 78 Higher levels of serum C-reactive protein (CRP) in middle-aged patients are also associated with an increased risk of AD and vascular dementia, which may indicate that inflammatory factors are a reflection of both dementia-related peripheral disease and cerebral mechanisms.…”

“…78 Higher levels of serum C-reactive protein (CRP) in middle-aged patients are also associated with an increased risk of AD and vascular dementia, which may indicate that inflammatory factors are a reflection of both dementia-related peripheral disease and cerebral mechanisms. 78 Of note is the fact that these processes can be measured long before manifestations of dementia begin to be observed. Follow-up studies in the elderly have also revealed a correlation between serum CRP levels and an increased incidence of dementia and AD.…”