Multisession gamma tACS modulates extracellular vesicle dynamics

Recent literature has demonstrated alterations in gamma-band oscillations in patients with Alzheimer's disease (AD), implicated in deficits in memory, neural communication, and synaptic plasticity [1]. Dysregulation of gamma oscillations can be modulated through different approaches, including sensory and electrical stimulation [1,2]. Among these, transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique capable of entraining endogenous oscillatory activity to an externally applied alternating current at a specific frequency [3]. In a double-blind, randomized, sham-controlled clinical trial, it was recently demonstrated that multisession gamma tACS applied over the precuneus resulted in significant clinical efficacy, cholinergic improvement, and gamma entrainment in patients with mild AD [4]. However, the biological mechanisms underlying its clinical efficacy remain largely unknown. Notably, no significant effects were observed in blood-based markers of AD pathology, including phosphorylated tau 217 (p-tau217), markers of neurodegeneration such as neurofilament light chain (NfL), or markers of astroglial activation such as glial fibrillary acidic protein (GFAP) [4].