Presymptomatic Treatment With Andrographolide Improves Brain Metabolic Markers and Cognitive Behavior in a Model of Early-Onset Alzheimer’s Disease

摘要: Alzheimer's disease (AD) is the most common type of dementia. The onset and progression this pathology are correlated with several changes in brain, including formation extracellular aggregates amyloid-beta (Aβ) peptide intracellular accumulation hyperphosphorylated tau protein. In addition, dysregulated neuronal plasticity, synapse loss, a reduction cellular energy metabolism have also been described. Canonical Wnt signaling has shown to be downregulated AD. Remarkably, we showed previously that vivo inhibition accelerates appearance AD markers transgenic (Tg) wild-type (WT) mice. Additionally, found stimulates metabolism, which critical for ability promote recovery cognitive function Therefore, hypothesized activation canonical presymptomatic animal model would improve some symptoms. To explore latter, used mouse (J20 Tg) mild phenotype expression (high levels amyloid aggregates) studied effect andrographolide (ANDRO), an activator signaling. We administration ANDRO J20 Tg mice prevented markers. Moreover, treated animals improvement performance. At synaptic level, severe deficiencies presynaptic as determined by electrophysiological parameters, all were completely restored normal administration. Finally, analysis hippocampal synaptosomes electron microscopy revealed length synapses was treatment. Altogether, these data support idea during stages could represent interesting pharmacological strategy delay