HCRT and Alzheimer disease: For instance, a mouse model of amyloidosis-β with deletion of the core clock gene Bmal1 has demonstrated that loss of central circadian rhythms leads to disruption of daily hippocampal interstitial fluid amyloid-β oscillations and accelerates plaque accumulation.121Another study found that orexin regulates the hippocampal clock and circadian oscillation of AD risk genes.122Overall, circadian science is evolving and provides new insights into early detection and modulation of NDDs.