| First Author | Peng W | Year | 2016 |
| Journal | Neurobiol Dis | Volume | 93 |
| Pages | 215-25 | PubMed ID | 27234656 |
| Mgi Jnum | J:231726 | Mgi Id | MGI:5774856 |
| Doi | 10.1016/j.nbd.2016.05.015 | Citation | Peng W, et al. (2016) Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease. Neurobiol Dis 93:215-25 |
| abstractText | Glymphatic transport, defined as cerebrospinal fluid (CSF) peri-arterial inflow into brain, and interstitial fluid (ISF) clearance, is reduced in the aging brain. However, it is unclear whether glymphatic transport affects the distribution of soluble Abeta in Alzheimer's disease (AD). In wild type mice, we show that Abeta40 (fluorescently labeled Abeta40 or unlabeled Abeta40), was distributed from CSF to brain, via the peri-arterial space, and associated with neurons. In contrast, Abeta42 was mostly restricted to the peri-arterial space due mainly to its greater propensity to oligomerize when compared to Abeta40. Interestingly, pretreatment with Abeta40 in the CSF, but not Abeta42, reduced CSF transport into brain. In APP/PS1 mice, a model of AD, with and without extensive amyloid-beta deposits, glymphatic transport was reduced, due to the accumulation of toxic Abeta species, such as soluble oligomers. CSF-derived Abeta40 co-localizes with existing endogenous vascular and parenchymal amyloid-beta plaques, and thus, may contribute to the progression of both cerebral amyloid angiopathy and parenchymal Abeta accumulation. Importantly, glymphatic failure preceded significant amyloid-beta deposits, and thus, may be an early biomarker of AD. By extension, restoring glymphatic inflow and ISF clearance are potential therapeutic targets to slow the onset and progression of AD. |
