Table 1: Arguments for inflammation-driven onset of dementia.

PROsCONs

Cell culturesAβ-stimulated microglia produce and secret a number of proinflammatory molecules and neurotoxic factors [59]
Pro-inflammatory cytokines attenuate microglial phagocytosis stimulated by fAβ or complement receptor 3 [60]
IL-1β and TNF-α synergistically stimulate microglial NGF transcription release [61]

Animal modelsIL-1R blockade alleviates cognitive deficits, markedly attenuates tau pathology, and partly reduces certain fibrillar and oligomeric forms of amyloid-β [15]Prolonged central IL-1R blockade leads to a marked reduce in brain volume in transgenic mice [16]
TNF-R1 deletion leads to diminished Aβ plaque formation, reduced beta-secretase 1 levels and activity, and overall unimpaired cognition [18]3xTg-ADxTNF-RI/RII knockout mice exhibit enhanced amyloid and tau-related pathological features, due to reduced microglial-mediated uptake of extracellular amyloid-β peptide pools [62]

AD patientsMCI patients who later developed AD had higher serum levels of
(i) TNFRI [3638]  
(ii) soluble CD40 [40]
(iii) IL-1β [41]
than healthy controls
AchE inhibitors increase serum IL-4 levels [21]
AD patients treated with etanercept showed some improvement, but did not match the animal models results
Measurements of CSF/plasma cytokines are contradictory
CSF TGF-β is increased in AD [33]—a putative effort for neurorepair
It is common knowledge that AchE treatment only slows disease but does not stop or reverse its course

Abbreviations: IL: interleukin, TNF: tumor necrosis factor, NGF: nerve growth factor, CSF: cerebrospinal fluid, and AchE: acetylcholinesterase.