ANG1-7 as an intervention for Alzheimer's Disease.

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PROJECT SUMMARY The objective of this study is to evaluate the impact of orally delivering Lactobacillus paracasei genetically modified to express Angiotensin (1-7) (LP-A) on Alzheimer’s Disease (AD). Aim 1 will test the hypothesis that LP-A treatment at the onset of pathology will significantly slow or delay accumulation of pTau and Aβ, markers of inflammation, loss of noradrenergic axons, and hippocampal synaptic dysfunction in TgF344-AD rats that is dependent upon activation of Mas receptors. Aim 2 will test the hypothesis that LP-A treatment improves performance in hippocampus-dependent behavioral assays and decreases anxiety in TgF344-AD rats that is dependent upon activation of Mas receptors. ANTICIPATED IMPACT: To date, proven treatments for preventing age- and AD mediated cognitive decline are lacking, thus research on potentially efficacious interventions is desperately needed. This study holds tremendous potential for generating proof of concept data that an orally- provided intervention improves or prevents deficits in synaptic circuit and cognitive function. The work is significant because it addresses several clinical and public health problems deemed critical by the NIH. Innovations in the project include the conceptual approach using genetic engineering techniques to deliver therapeutic compounds in probiotic form, and the study design which lays the groundwork for future translation to humans to ultimately help address the massive health burden of AD related cognitive decline.