The role of inflammatory processes in Alzheimer’s disease

Abstract

It has become increasingly clear that inflammatory processes play a significant role in the pathophysiology of Alzheimer's disease (AD). Neuroinflammation is characterized by the activation of astrocytes and microglia and the release of proinflammatory cytokines and chemokines. Vascular inflammation, mediated largely by the products of endothelial activation, is accompanied by the production and the release of a host of inflammatory factors which contribute to vascular, immune, and neuronal dysfunction. The complex interaction of these processes is still only imperfectly understood, yet as the mechanisms continue to be elucidated, targets for intervention are revealed. Although many of the studies to date on therapeutic or preventative strategies for AD have been narrowly focused on single target therapies, there is accumulating evidence to suggest that the most successful treatment strategy will likely incorporate a sequential, multifactorial approach, addressing direct neuronal support, general cardiovascular health, and interruption of deleterious inflammatory pathways.

Amyloidosis Associated with Cerebral Amyloid Angiopathy: Cell Signaling Pathways Elicited in Cerebral Endothelial Cells

“…Compared to microvessels from age-matched controls, AD brain microvessels release significantly higher levels of a number of inflammatory factors including nitric oxide, thrombin, TNF-α, transforming growth factor-β, IL-1β, IL-6, IL-8, and matrix metalloproteinases [71–74]. The latter comprises a multifactorial family of proteins capable of affecting disease pathogenesis through various mechanisms including disruption of permeability barriers and regulation of the activity of factors indispensable for neuronal survival such as NGF [75]. In contrast to the detailed Aβ-mediated cell death pathways illustrated above, the specific mechanisms elicited by the diverse inflammatory mediators involved in CAA-related paths, remain to be clearly defined and are likely to differ depending on the specific inflammatory elements/pathways affected.…”

Peripheral complement interactions with amyloid β peptide: Erythrocyte clearance mechanisms

“…For example, failure to clear Aβ from blood could lead to an unfavorable concentration gradient for movement of Aβ out of the brain [3]. Moreover, the propensity of fluid-phase Aβ to form insoluble fibrils and to activate complement and other inflammatory mediators could well play a role in the co-localization of inflammatory mediators with the vascular abnormalities that are observed in Alzheimer’s disease (AD) [reviewed in 6,7]. Mackic and colleagues [8,9] have provided critical data on serum and organ levels of Aβ after its intravenous inoculation into the bloodstream of non-human primates (NHPs).…”

The Evaluation of Neutrophil-Lymphocyte Ratio in Alzheimer’s Disease

“…There is growing consensus in the literature that inflammation plays a significant role in the pathophysiology of Alzheimer's disease (AD) [1]. AD, the most common cause of dementia, is a progressive neurodegenerative disorder with uncertain pathogenesis that mainly affects the elderly population [2][3][4].…”