We have previously shown a precocious and selective dopamine neurodegeneration in the Ventral Tegmental Area (VTA) of Tg2576 mice, a reliable experimental model of Alzheimer’s Disease (AD). In this model, the VTA neuronal loss causes the decrease of dopamine outflow in the Hippocampus and the Nucleus Accumbens, leading to impaired synaptic plasticity, memory and reward processing. Mesocorticolimbic system deficits are also reported in AD patients. Interestingly, pharmacological interventions aimed at improving DA levels ameliorate AD deficits in mice.However, drug-based treatments might cause important side-effects in patients, underscoring the need for alternative methods to modulate the dopaminergic system effectively. Transcranial Direct Current Stimulation (tDCS), a non-pharmacological and non-invasive technique devoid of side-effects, showed effectiveness in activating the mesocorticolimbic system by enhancing VTA activity when delivered over prefrontal cortex both in rodents and patients. Yet, investigations of tDCS as a potential tool to treat AD are still at a conceptual stage.Here, we explored whether a 10-day prefrontal-tDCS in Tg2576 mice could promote the recovery of neurochemical, functional, morphological and behavioural deficits by enhancing DA levels.We demonstrated that this treatment increases hippocampal dopamine levels, restores synaptic plasticity, and improves declarative memory in Tg2576 mice. Prefrontal-tDCS also reduces depressive-like behaviours and locomotor hyperactivity, two non-cognitive features of Tg2576 mice. Finally, tDCS-treated mice showed reduced hippocampal neuroinflammation and amyloid plaque burden.Overall, these results suggest that prefrontal-tDCS, modulating dopaminergic system, may be a promising interventional tool to counteract several AD deficits, emerging as a valuable ally in the fight against AD.