Electrophysiological markers of early Alzheimer’s Disease proteinopathy in the human brain

Alzheimer's Disease (AD) is characterized by the pathological accumulation of amyloid‐beta (Aβ) and hyperphosphorylated tau proteins in the brain. Animal models have demonstrated that early Aβ accumulation induces neuronal hyperexcitability (Stargardt et al., 2015), whereas later additive effects of Aβ and tau lead to suppression of neuronal activity that parallels disease severity (Busche et al., 2020). Although neural hypo‐excitability has been reported in the later stages of AD, it remains unknow if such a shift from hyper‐ to hypo‐excitability exists at the macroscopic level in the human brain of asymptomatic individuals (Figure 1).