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Review
. 2015 Apr 17:12:74.
doi: 10.1186/s12974-015-0291-y.

Rodent models of neuroinflammation for Alzheimer's disease

Amir Nazem  1 , Roman Sankowski  2 , Michael Bacher  3 , Yousef Al-Abed  4
Affiliations
Review

Rodent models of neuroinflammation for Alzheimer's disease

Amir Nazem et al. J Neuroinflammation. .

Abstract

Alzheimer's disease remains incurable, and the failures of current disease-modifying strategies for Alzheimer's disease could be attributed to a lack of in vivo models that recapitulate the underlying etiology of late-onset Alzheimer's disease. The etiology of late-onset Alzheimer's disease is not based on mutations related to amyloid-β (Aβ) or tau production which are currently the basis of in vivo models of Alzheimer's disease. It has recently been suggested that mechanisms like chronic neuroinflammation may occur prior to amyloid-β and tau pathologies in late-onset Alzheimer's disease. The aim of this study is to analyze the characteristics of rodent models of neuroinflammation in late-onset Alzheimer's disease. Our search criteria were based on characteristics of an idealistic disease model that should recapitulate causes, symptoms, and lesions in a chronological order similar to the actual disease. Therefore, a model based on the inflammation hypothesis of late-onset Alzheimer's disease should include the following features: (i) primary chronic neuroinflammation, (ii) manifestations of memory and cognitive impairment, and (iii) late development of tau and Aβ pathologies. The following models fit the pre-defined criteria: lipopolysaccharide- and PolyI:C-induced models of immune challenge; streptozotocin-, okadaic acid-, and colchicine neurotoxin-induced neuroinflammation models, as well as interleukin-1β, anti-nerve growth factor and p25 transgenic models. Among these models, streptozotocin, PolyI:C-induced, and p25 neuroinflammation models are compatible with the inflammation hypothesis of Alzheimer's disease.

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Figures

Figure 1
Figure 1
Time course of pathological events in models compatible with inflammation hypothesis of Alzheimer’s disease. In the models shown, neuroinflammation starts prior to the appearance of AD related lesions (hp-Tau and Aβ depositions). Animals develop cognitive deficits at variable time points after the induction of neuroinflammation in the respective models. In contrast to the most of transgenic AD animal models, the STZ and p25 Tg models of neuroinflammation feature neurodegeneration. It is noteworthy that the PolyI:C model has the longest time lapse between induction of neuroinflammation and cognitive deficits. Note that the time points do not necessarily represent the actual time of appearance, but the time points when the pathological hallmarks were detected in the respective references (Abbreviations: LPS lipopolysaccharide; PolyI:C polyriboinosinic-polyribocytidilic acid; p25 Tg p25 transgenic model; IL-1β Tg: interleukin-1β transgenic model; ICV-STZ intracerebroventricular streptozotocin model; hp-Tau hyperphosphorylated tau; Aβ amyloid-β).
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