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.
Highlights
IntroductionAlzheimer’s disease (AD) remains incurable and is considered a major human healthcare challenge [1]
After decades of research, Alzheimer’s disease (AD) remains incurable and is considered a major human healthcare challenge [1]
We focused on characterizing the models suitable for studying the inflammation hypothesis of Alzheimer’s disease, based on which neuroinflammation is considered as the driving force of AD pathology and starts early in the course of the disease, prior to tau hyperphosphorylation and amyloid plaque formation [23,13]
Summary
Alzheimer’s disease (AD) remains incurable and is considered a major human healthcare challenge [1]. All of the ensuing phase three clinical trials have failed [3] These failures question our accurate understanding of the disease [1], based on Failure in AD drug discovery may in part be attributable to the so-called lesion seduction [1], a simplistic paradigm postulating that AD-related histopathological lesions are a direct reflection of its etiology [1]. Following this paradigm, the most commonly used animal models of AD are designed to recapitulate the lesions of AD [5], namely amyloid-β (Aβ) plaques and neurofibrillary tangles through transgenic induction of mutations related to amyloid and tau production (amyloid precursor protein (APP), presenilin-1 (PS1) and PS2, or tau mutations [6,1,7]). Since late-onset AD (LOAD) is not caused by such mutations [6], the results from these animal models cannot be reliably extrapolated to the human condition, further widening the gap between human AD pathology and its most commonly used models
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
