Role of neuroinflammation in neurodegeneration: new insights

Abstract

Previously, the contribution of peripheral infection to cognitive decline was largely overlooked however, the past 15 years have established a key role for infectious pathogens in the progression of age-related neurodegeneration. It is now accepted that the immune privilege of the brain is not absolute, and that cells of the central nervous system are sensitive to both the inflammatory events occurring in the periphery and to the infiltration of peripheral immune cells. This is particularly relevant for the progression of Alzheimer’s disease, in which it has been demonstrated that patients are more vulnerable to infection-related cognitive changes. This can occur from typical infectious challenges such as respiratory tract infections, although a number of specific viral, bacterial, and fungal pathogens have also been associated with the development of the disease. To date, it is not clear whether these microorganisms are directly related to Alzheimer’s disease progression or if they are opportune pathogens that easily colonize those with dementia and exacerbate the ongoing inflammation observed in these individuals. This review will discuss the impact of each of these challenges, and examine the changes known to occur with age in the peripheral immune system, which may contribute to the age-related vulnerability to infection-induced cognitive decline.

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

“…Neuroinflammation is known to directly and systemically contribute to the recruitment of peripheral inflammatory cells and increase BBB permeability in the neurodegenerative diseases (Hayley and Anisman, 2005; Ferrari and Tarelli, 2011; Espinosa-Oliva et al, 2014; Dendrou et al, 2016; McManus and Heneka, 2017; Schain and Kreisl, 2017). Peripheral infection and inflammation increases BBB permeability and neuroinflammation in the animal model of AD (Takeda et al, 2013).…”

Association Between Periodontitis and Amyloid β Peptide in Elderly People With and Without Cognitive Impairment

“…Concern is growing about the expected rise in cases of dementia and, specifically, Alzheimer disease, 1,2 whose physiopathology 1 and treatment 3 have not yet been completely established. However, there appears to be wide consensus that development of Alzheimer disease is attributable not only to a disorder in amyloid β (Aβ) metabolism but also to inflammation of the brain and vascular damage 4‐6 . According to the “amyloid hypothesis,” anomalous accumulation of Aβ peptide in certain brain areas leads to neuronal dysfunction and subsequent neuron death 7 .…”

Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography

“…Additionally, the time course of such processes and their role in comparison to a direct transfer of folate, folate conjugates and analogues across the blood vessels would be an important item for the estimation of a potential diagnostic value of FR ligands in clinical PET imaging methods. Moreover, the recognition that the permeability of the blood brain barrier increases with rising age earns some attention [141].…”