Table 1.

Arguments for inflammation-driven onset of dementia.

	PROs	CONs
Cell cultures	Aβ-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 models	IL-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 patients	MCI patients who later developed AD had higher serum levels of (i) TNFRI [36–38]   (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.