Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Aβ load chronically, as demonstrated in vivo

Iaccarino et al. (2016) [1] exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer’s Disease (AD) mouse models, generating action potentials at 40 Hz, activating ∼54% of microglia to colocalize with Aβ plaque, acutely, and clearing ∼ 50% of Aβ plaque after seven days, but only in the visual cortex. Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) [1] but throughout its area of application. We exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 μs-long pulses, spatial peak pulse average value of 190 W/cm2). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days. Acute application of tFUS activated more microglia that colocalized with Aβ plaque relative to sham ultrasound (36.0 ± 4.6% versus 14.2 ± 2.6% [mean ± standard error], z = 2.45, p