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| Publication(s) | Type of Study | Observations |
|
| Wisniewski et al., 1989 [1], 1992 [2]; Frackowiak et al., 1992 [3] | Neuropathologic | Microglia are “frustrated phagocytes” responsible for manufacture of amyloid fibrils and not for their removal. |
| Meda et al., 1995 [15] | In vitro | Activated microglia secrete proinflammatory cytokines that promote neural injury at high levels. |
| Tan et al., 1999 [16] | Mouse models | Aβ and CD40L-stimulated microglia release TNF-α that injures primary cortical neurons. CD40 ligand-deficient Tg2576 mice have reduced microglial activation and tau hyperphosphorylation. |
| McGeer et al. 1990 [18], 1992 [19], 1996 [20] | Epidemiologic | There is lower incidence of dementia in elderly patients with arthritis compared to the general population. |
| Mackenzie and Munoz, 1998 [21] | Neuropathologic | Chronic NSAID users with senile plaques have 3-fold less activated microglia than non-users. |
| Szekely et al., 2004 [23] | Epidemiologic | Systematic review of over 25 epidemiologic studies shows ~50% reduced risk of AD associated with NSAID use. |
| Lim et al., 2000 [24], 2001 [72] | Mouse models | NSAID-treated Tg2576 mice have significantly reduced amyloid deposition, astrogliosis, and IL-1β abundance. |
| Jantzen et al., 2002 [25]; Yan et al., 2003 [26]; Heneka et al., 2005 [27] | Mouse models | Ibuprofen-treated Tg2576, APP/PS1 or APPV717I transgenic mice have reduced microglial activation and amyloid deposits. |
| Tan et al., 2002 [30] | Mouse models | Genetic or pharmacologic ablation of CD40 ligand in Tg2576 mice reduces cerebral amyloidosis and mitigates gliosis. |
| Townsend et al., 2005 [31] | In vitro | CD40 ligand in the presence of Aβ (1–42) promotes a microglial proinflammatory antigen presenting cell phenotype. |
| Qiao et al., 2001 [32] | Mouse models | Chronic intracerebroventricular injection of LPS accelerates Aβ plaque load in APPV717F transgenic mice. |
| Mori et al., 2010 [33] | Mouse models | Forcing expression of proinflammatory S100B accelerates glial activation and cerebral amyloid pathology in Tg2576 mice. |
| Fuhrmann et al., 2010 [34] | Mouse models | Cx3cr1 endorses microglial-mediated neuronal loss in 3xTg AD mice. |
| Lee et al., 2010 [36] | Mouse models | Cx3cr1 deficiency reduces cerebral amyloid and reactive microglia in APP/PS1 and R1.40 mice. Cx3cr1−/− microglia have greater Aβ uptake. |
| Sundaram et al., 2012 [38] | Mouse models | Neuroinflammation occurs early and promotes neurodegeneration mediated by lysophosphatidylcholine and Cdk5/p25. Inducible p25 expression in vivo triggers neuroinflammation and intraneuronal Aβ. |
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