Research published today in Biomed Central’s open access journal Journal of Neuroinflammation suggests that chronic inflammation can predispose the brain to develop Alzheimer’s disease.
To date it has been difficult to pin down the role of inflammation in Alzheimer’s disease (AD), especially because trials of NSAIDs appeared to have conflicting results. Although the ADAPT (The Alzheimer`s Disease Anti-inflammatory Prevention Trial) trial was stopped early, recent results suggest that NSAIDs can help people with early stages of AD but that prolonged treatment is necessary to see benefit.
Researchers from the University of Zurich, in collaboration with colleagues from the ETH Zurich and University of Bern investigated what impact immune system challenges (similar to having a severe viral infection) would have on the development of AD in mice. Results showed that a single infection before birth (during late gestation) was enough to induce long-term neurological changes and significant memory problems at old age.
These mice had a persistent increase in inflammatory cytokines, increased levels of amyloid precursor protein (APP), and altered cellular localization of Tau. If this immune system challenge was repeated during adulthood the effect was strongly exacerbated, resulting in changes similar to those seen for pathological aging.
Dr Irene Knuesel who led this research explained, “The AD-like changes within the brain of these mice occurred without an increase in amyloid β (Aβ). However, in mice genetically modified to produce the human version of Aβ, the viral-like challenge drastically increased the amount of Aβ at precisely the sites of inflammation-induced APP deposits. Based on the similarity between these APP/A aggregates in mice and those found in human AD, it seems likely that chronic inflammation due to infection could be an early event in the development of AD.
You and your readers may be interested to know that a new anti-inflammatory substance was shown to ameliorate the simulated Alzheimer’s disease (AD) in a mouse model, such as cited in your article, in a peer reviewed study last year. The particulars (abstract) are below.
This same substance, anatabine citrate, is already available (because of its known safety) in a “dietary supplement” … “OTC” … called Anatabloc (see Anatabloc.com) in the U.S. and 47 other countries. Clinical trials are underway to confirm efficacy in humans.
Anatabine citrate is apparently unique in its direct action on the NF-kB inflammatory pathway … thus avoiding the problem side-effects associated with “NSAIDS” … and allowing continual use to treat or prevent excess inflammation in most bodily systems.
This also has been shown to help MS in a mouse model.
It has been anecdotally reported (all research is just getting underway … the discovery of this anti-inflammatory is only a couple of years old) to aid in a lengthy list of autoimmune and other disorders, such as Crohn’s, ulcerative colitis, asthma, etc.
It also is reported anecdotally to aid in quick recovery from injury, such as muscle overuse/work in sports, etc.
Ladenson et. al. in an endocrinology group at Johns Hopkins believe it may be the first and only treatment for Hashimoto’s (autoimmune) thyroiditis, and trials on that front are now underway.
This may promise a whole new approach, allowing continual treatment, for the now recognized problem of chronic excessive inflammatory reaction.
The particulars about the in vivo AD study in mice follows:
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Author(s)
Paris, D., Beaulieu-Abdelahad, D., Bachmeier, C., Reed, J., Ait-Ghezala, G., Bishop, A., Chao, J., Mathura, V., Crawford, F., Mullan, M.,
Journal
European Journal of Pharmacology
Vol. 670, No. 2, pages 384-391 (2011)
DOI: 10.1016/j.ejphar.2011.09.019
ISSN
0014-2999
Publisher
Elsevier
Abstract
Brain A@b accumulation represents a key pathological hallmark in Alzheimer*s disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on A@b production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer*s disease. In vitro, anatabine lowers A@b”1″-“4″0 and A@b”1”-“4″2 levels in a dose dependent manner and reduces sAPP@b production without impacting sAPP@a levels suggesting that anatabine lowers A@b production by mainly impacting the @b-cleavage of APP. Additionally, we show that anatabine lowers NF@kB activation at doses that inhibit A@b production in vitro. Since NF@kB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for A@b production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the A@b lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble A@b”1”-“4″0 and A@b”1”-“4″2 levels in a transgenic mouse model of Alzheimer*s disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain A@b accumulation.