Inflammaging as a prodrome to Alzheimer's disease

Recently, the term "inflammaging" was coined by Franceshci and colleagues to characterize a widely accepted paradigm that ageing is accompanied by a low-grade chronic up-regulation of certain pro-inflammatory responses. Inflammaging differs significantly from the traditional five cardinal features of acute inflammation in that it is characterized by a relative decline in adaptive immunity and T-helper 2 responses and is associated with increased innate immunity by cells of the mononuclear phagocyte lineage. While the over-active innate immunity characteristic of inflammaging may remain subclinical in many elderly individuals, a portion of individuals (postulated to have a "high responder inflammatory genotype") may shift from a state of "normal" or "subclinical" inflammaging to one or more of a number of age-associated diseases. We and others have found that IFN-γ and other pro-inflammatory cytokines interact with processing and production of Aβ peptide, the pathological hallmark feature of Alzheimer's disease (AD), suggesting that inflammaging may be a "prodrome" to AD. Although conditions of enhanced innate immune response with overproduction of pro-inflammatory proteins are associated with both healthy aging and AD, it is suggested that those who age "well" demonstrate anti-inflammaging mechanisms and biomarkers that likely counteract the adverse immune response of inflammaging. Thus, opposing the features of inflammaging may prevent or treat the symptoms of AD. In this review, we fully characterize the aging immune system. In addition, we explain how three novel treatments, (1) human umbilical cord blood cells (HUCBC), (2) flavanoids, and (3) Aβ vaccination oppose the forces of inflammaging and AD-like pathology in various mouse models

Inhibition of both p38 and/or p44/42 pathways further enhances CD45RB cross-linking mediated microglial phagocytosis of Aβ_1–42 peptide.

<p>Microglial treatment conditions are indicated and are further described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002135#s4" target="_blank">Material and Methods</a>. (A) Cell supernatants and lysates were analyzed for extracellular (top panel) and cell-associated (bottom panel) FITC-Aβ_1–42 using a fluorometer. Data are represented as the relative fold of mean fluorescence change (mean±SD), calculated as the mean fluorescence for each sample at 37°C divided by mean fluorescence at 4°C (n = 6 for each condition presented). Cell lysates (B, C) were assayed for microglial phagocytosis of Aβ_1–42 peptide by Aβ-ELISA. Results are reported as picogram per microgram of total protein for cells incubated at 37°C over cells incubated at 4°C. (37°C/4°C; n = 3 for each condition presented). One-way ANOVA followed by <i>post hoc</i> Bonferroni testing revealed significant between-group differences (*<i>P</i><0.05, **<i>P</i><0.001) and CD45RB Ab compared with isotype-control IgG, <i>P</i><0.001. Note: SB = SB203580, PD = PD98059, Ab = antibody, pp = phosphorylatioin.</p