Jahnavi Udaikumar

Introduction. Alzheimer’s disease (AD), the most common form of dementia, affects nearly 45 million people worldwide with increasing progression despite its unclear etiology.¹ Discovered in 1906, AD is a neurodegenerative disorder that arises from accumulations of amyloid-β plaques and tau tangles, eventually resulting in blocked cell-to-cell communication at neuronal synapses and post-translational modifications. ² Hence, former treatments affected amyloid-β fibril buildup while recent studies have explored the various pathogenic mechanisms of tau neurofibrillary tangles in several mice models. While some studies have attacked tau’s hyper-phosphorylated involvement with proto-oncogene tyrosine-protein kinase, other studies have attacked the tau gene p38γ-mediated inhibition of Aβ. ³ These findings could suggest a tau as a potential therapeutic target for AD. Methods. The triple transgenic AD mice (3xTg-AD) model was used. These mice, expressing the mutant tauP301L gene, were treated with 6 μg/ml Se-Met (Sigma-Aldrich) in their drinking water for 12 weeks, while the control mice and wild-type mice received normal drinking water. Following this treatment, the three different groups of mice were subject to different cognitive ability testing and plasma tau measurement. ⁴ Results. For the Morris water maze cognition test, the three different mice groups, escape latencies of the 3xTg-AD mice were markedly longer than those of the wild-type, however reversed with Se-Met treatment. The step-down passive avoidance test was also used to evaluate the effect of Se-Met on the learning and memory of the transgenic mice.⁴ Compared with WT mice, 3xTg-AD mice exhibited a poor performance consisting of a significant increase in the number of errors Se-Met treatment did not significantly affect the SDL of 3xTg-AD mice, but the number of errors was significantly decreased. After 3 months of treatment with Se-Met, Western blot analysis of total tau levels showed significant reductions in Tris-buffered saline (TBS)-soluble and TBS-insoluble tau in the hippocampus and cortex in Se-Met-treated mice. Similarly, neuronal staining using a specific antibody against pS404-tau revealed lower fluorescence intensity in the hippocampus of Se-Met-treated mice than in control mice. ⁴ Conclusion. Studies have shown that a significant portion of AD etiology is contributable to tau neurofibrillary tangle buildup, mainly through hyper-phosphorylation, autophagy and Aβ excitotoxity.^5,6 Hence, treatments directed at tau protein pathogenesis steps would be effective in reducing AD prognosis and symptoms, as demonstrated by the Se-Met study among others.

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