Inflammation and Microglia Actions in Alzheimer’s Disease

Abstract

A variety of studies have documented increased presence of reactive microglia in the brains of not only Alzheimer's disease (AD) patients but its transgenic mouse models. Since these cells are often characterized in association with fibrillar Abeta peptide-containing plaques, it has been assumed that plaque interaction provides one stimulus for the phenotype observed. The growing appreciation that microglia phenotype changes with age and that resident immune cells are commingled with blood-derived macrophage has complicated understanding of the behavior of these cells in AD. In addition, comparison of microglia within AD brains and the many rodent models suggests that there are population phenotype differences among these cells within any given brain during disease. Recent immunomodulatory strategies that have been employed, although effective at improving behavioral performance, decreasing Abeta plaque load, and altering immune molecule levels, have not yet resolved the details and dynamics of the microglial and macrophage responses. The heterogeneity of microglial presentation in AD brains and its transgenic mouse models and the outcomes of immunoregulatory efforts will be reviewed below along with the remaining question of how much understanding of microglial behavior is actually required in order to propose a microglia-related therapy for AD.

Imaging microglial activation and glucose consumption in a mouse model of Alzheimer's disease

“…In addition to non-invasive quantification of microglial activation, we aimed to investigate the correlation between neuroinflammation and neuronal function as determined by [ 18 conditions between AD and control mice, supporting our results. Only after inflicting neuronal damage to the locus coeruleus, a significant difference between the two animal groups could be observed.…”

“…Initially, they take on a neuroprotective role by releasing amyloid-degrading enzymes for the clearance of amyloid fibrils in the early stages of the disease. As the disease progresses, however, these neuroprotective clearing mechanisms are insufficient or too slow to counteract the deposition of Aβ in the AD brain, but the production of the neurotoxic pro-inflammatory molecules is preserved, maintaining chronic neuroinflammation and resulting in neurodegeneration (Cameron and Landreth, 2010;Combs, 2009;Rogers et al, 2002;Sastre et al, 2006).…”

Interaction between Amyloid-β Pathology and Cortical Functional Columnar Organization

“…Brain injuries are known to be a major risk factor for Alzheimer's and other neurodegenerative diseases (Herrup;DeKosky et al, 2007;Adibhatla and Hatcher, 2008;Pluta and Amek, 2008;Härtig et al, 2009). It may be that plaques could be considered as a type of brain injury, disrupting the cytoarchitecture (Knowles et al, 1998;Knowles et al, 1999), being generally neurotoxic (Urbanc et al, 2002;Velez-Pardo et al, 2004;Floden et al, 2005;Spires et al, 2005;Naylor et al, 2008a,b), and causing a general immune response (Eikelenboom et al, 2006;Garcia-Alloza et al, 2007;Meyer-Luehmann et al, 2008;Combs, 2009;Mundt et al, 2009;Salmina, 2009).…”

High-Fat and Cholesterol Intake Affects Brain Homeostasis and Could Accelerate the Development of Dementia: A Systemic View

“…It suggested there is another mechanism elucidating the cognitive impairment related to consumption of diets rich in fat; a good candidate is brain inflammation. Chronic inflammation is one of the principal altered events associated with AD [48], and it has been linked to obesity and has been reported that there is a correlation between both, obesity and AD [49,50]. Middle-aged C57BL6 male mice were fed for 21 weeks with chow equivalent to Western diet containing 41% fat or a high-fat lard diet containing 60% fat for 16 weeks.…”