Anatabine, a natural alkaloid found in plants of the Solanacea family, has a chemical structure closely related to nicotine and is a full agonist of α7 and α4β2 nicotinic acetylcholine receptors (nAChR).  Previous studies have found that anatabine possesses anti-inflammatory properties that may be  related to its activity in reducing the activation of the NFκB and STAT3 transcription factors,  which regulate the expression of a large array of inflammatory genes including cytokines such as IL1, IL-6, TNFα and inducible nitric oxide synthase (iNOS).

In the present study the authors investigated the efficacy of chronic anatabine treatment on the AD –related phenotypes (e.g., pathological Aβ deposits, neuroinflammation and behavioral deficits) observed in the APPswe/PS1 transgenic mouse model. In order to model therapeutic intervention in mild to moderate AD rather than a prophylactic approach anatabine treatment was initiated in 10 month-old mice, an age at which they already present significant Aβ deposits and cognitive impairments. Mice received doses of 10 mg/Kg/Day or 20 mg/Kg/Day, the latter had been previously found to reduce neuroinflammation in several mouse models of CNS inflammation. Behavioral studies found that 6 ½  months of chronic oral anatabine treatment suppressed the hyperactivity and disinhibition observed in the  APPswe/PS1 Tg mice compared to  APPswe/PS1 Tg mice receiving regular drinking water. In addition, anatabine treatment alleviated the profound social interaction and social memory deficits observed in Tg mice. Biochemical analysis found that anatabine treatment reduced the activation of STAT3 and NFκB in the vicinity of Aβ deposits, which correlated with a reduction in the expression of some of target genes of these transcription factors including Bace1, iNOS and Cox-2.Neuropathological analysis revealed a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brains of APPswe/PS1 Tg mice treated with anatabine. Taken together these  data show that  chronic oral treatment with anatabine reduced β-amyloidosis and neuroinflammation and alleviated some behavioral impairments observed in Tg  mice, supporting further exploration of anatabine as a possible disease modifying agent for the treatment of AD.