Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice

T Cells—Protective or Pathogenic in Alzheimer’s Disease?

“…2). Indeed it was recently found that TNFα + or IL-1β + microglia have a lower Aβ load than non-TNFα-or IL-1β-producing cells in the brains of 21 month-old APP/PS1 mice (Babcock et al 2015). This is in line with other reports demonstrating poor Aβ-associated phagocytic function in microglia in AD (Frackowiak et al 1992).…”

“…There is an increase in circulating activated CD4 + and CD8 + T cells in AD patients (Lueg et al 2015) and T cells from AD patients are skewed to Th17 and Th9 phenotypes (Saresella et al 2011). An increase in circulating IFN-γ-secreting CD4 + and CD8 + T cells has also been reported in AD patients (Baglio et al 2013;Fiala et al 2005) with a decrease in CD4 + PD-1 + T cells, indicating a resistance to apoptosis (Saresella et al 2012). The memory status of these cells is also affected, with decreased levels of naïve T cells and a corresponding increase in effector memory or terminallydifferentiated CD4 + and CD8 + T cells in AD patients compared with age-matched controls (Larbi et al 2009;Pellicano et al 2012;Saresella et al 2011;Schindowski et al 2007;Speciale et al 2007).…”

Microglia in Alzheimer’s disease

“…Microglia producing IL-1α and IL-1Rα showed a higher phagocytic index and Aβ load than microglia that did not produce these cytokines. Interestingly, TNF-α-and IL-1β-producing microglia were abundant in APP/PS1dE9 AD model mice and were associated with lower Aβ load and phagocytic index (79). However, most experimental data concerning microglial Aβ phagocytosis published to date must be considered with great care, as the assays used measured mostly uptake but not intracellular Aβ degradation.…”

Telomere dysfunction reduces microglial numbers without fully inducing an aging phenotype

“…Our finding that the volume reduction of the dentate gyrus was apparent not just in 6-to 7-month-old but also in 2-to 3-month-old G3 KO mice, suggests that the dentate gyrus of G3 KO mice never fully attains the volume of normal adult WT mice. In evaluating the use of the G3 TERC KO mouse as a model of accelerated aging, it should be noted that normal aging is not usually associated with a reduction of the cerebral cortex volume in the mouse (Babcock et al, 2015). Interestingly, however, when we studied the G2 KO mice, we found that this mouse had normal microglial numbers, but a significantly reduced dentate gyrus volume.…”

“…In vivo 2-photon laser-scanning microscopy showed that the distal branches of "resting", ramified microglia have highly motile fine protrusions, allowing microglial cells to continually survey the cellular environment (Davalos et al, 2005;Nimmerjahn et al, 2005). Dead cells or cellular debris are thereby rapidly taken up and cleared from the neuropil by surveying microglia (Babcock et al, 2015;El Khoury et al, 1996;Hickman et al, 2008;Nielsen et al, 2009).…”