| First Author | Roh JH | Year | 2012 |
| Journal | Sci Transl Med | Volume | 4 |
| Issue | 150 | Pages | 150ra122 |
| PubMed ID | 22956200 | Mgi Jnum | J:188120 |
| Mgi Id | MGI:5439204 | Doi | 10.1126/scitranslmed.3004291 |
| Citation | Roh JH, et al. (2012) Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of beta-Amyloid in Mice with Alzheimer's Disease Pathology. Sci Transl Med 4(150):150ra122 |
| abstractText | Aggregation of beta-amyloid (Abeta) in the brain begins to occur years before the clinical onset of Alzheimer's disease (AD). Before Abeta aggregation, concentrations of extracellular soluble Abeta in the interstitial fluid (ISF) space of the brain, which are regulated by neuronal activity and the sleep-wake cycle, correlate with the amount of Abeta deposition in the brain seen later. The amount and quality of sleep decline with normal aging and to a greater extent in AD patients. How sleep quality as well as the diurnal fluctuation in Abeta change with age and Abeta aggregation is not well understood. We report a normal sleep-wake cycle and diurnal fluctuation in ISF Abeta in the brain of the APPswe/PS1deltaE9 mouse model of AD before Abeta plaque formation. After plaque formation, the sleep-wake cycle markedly deteriorated and diurnal fluctuation of ISF Abeta dissipated. As in mice, diurnal fluctuation of cerebrospinal fluid Abeta in young adult humans with presenilin mutations was also markedly attenuated after Abeta plaque formation. Virtual elimination of Abeta deposits in the mouse brain by active immunization with Abeta(42) normalized the sleep-wake cycle and the diurnal fluctuation of ISF Abeta. These data suggest that Abeta aggregation disrupts the sleep-wake cycle and diurnal fluctuation of Abeta. Sleep-wake behavior and diurnal fluctuation of Abeta in the central nervous system may be functional and biochemical indicators, respectively, of Abeta-associated pathology. |
