Transcranial direct current stimulation does not improve memory deficits or alter pathological hallmarks in a rodent...

Alzheimer's disease (AD) is a progressive and debilitating degenerative disorder for which there are currently no effective therapeutic options. Non-invasive neuromodulation, including transcranial direct current stimulation (tDCS), has been investigated for the treatment of cognitive symptoms in AD. Results from clinical and preclinical studies, however, have been somewhat controversial. We investigate whether tDCS delivered to triple transgenic (3xTg) AD mice improves memory deficits and mitigates the development of AD-type neuropathology. 3xTg AD mice and controls were implanted with paddle electrodes over the skull. The cathode was anterior to bregma and the anode anterior to lamda. tDCS was delivered for 20 min/day, 5 days/week over three weeks at 50 μA. Though this amplitude was lower than the one used in the preclinical literature, it generated a high current density compared to the clinical scenario. Memory testing was conducted during treatment weeks 2 and 3. Post-mortem pathological AD markers were studied. Our results show that performance of 3xTg mice in the novel object recognition and Morris water maze tests was significantly impaired compared to that of controls. In addition, AD transgenics had an increased expression of tau, phosphorylated-tau and amyloid precursor protein in the hippocampus. tDCS did not improve behavioural deficits or mitigated the development of AD neuropathology in 3xTg animals. In summary, we found that tDCS at the settings selected in our study was largely ineffective in improving memory performance or altering the expression of AD pathological hallmarks in a validated mouse model.