| First Author | Davis J | Year | 2006 |
| Journal | Neurobiol Aging | Volume | 27 |
| Issue | 7 | Pages | 946-54 |
| PubMed ID | 16105708 | Mgi Jnum | J:108851 |
| Mgi Id | MGI:3625200 | Doi | 10.1016/j.neurobiolaging.2005.05.031 |
| Citation | Davis J, et al. (2006) Deficient cerebral clearance of vasculotropic mutant Dutch/Iowa Double Ass in human AssPP transgenic mice. Neurobiol Aging 27(7):946-54 |
| abstractText | Cerebral amyloid angiopathy (CAA) is a prominent pathological feature of Alzheimer's disease and related familial CAA disorders. However, the mechanisms that account for the cerebral vascular accumulation of amyloid ss-peptide (Ass) have not been defined. Recently, we reported novel transgenic mice (Tg-SwDI) expressing neuronally derived Swedish/Dutch/Iowa vasculotropic mutant human Ass precursor (AssPP) that develop early-onset and robust accumulation of fibrillar cerebral microvascular Ass. Deficient clearance of Dutch/Iowa mutant Ass from brain across the capillary blood-brain barrier into the circulation may contribute to its potent cerebral accumulation. To further evaluate this theory, we generated a new transgenic mouse (Tg-Sw) that is nearly identical to Tg-SwDI, except lacking the Dutch/Iowa Ass mutations. Tg-Sw and Tg-SwDI mice expressed comparable levels of human AssPP in brain and not in peripheral tissues. However, Tg-SwDI mice strongly accumulated Dutch/Iowa mutant Ass in brain, particularly in the cerebral microvasculature, whereas Tg-Sw mice exhibited no accumulations of wild-type Ass. Conversely, Tg-SwDI mice had no detectable Dutch/Iowa mutant Ass in plasma whereas Tg-Sw mice exhibited consistent levels of human wild-type Ass in plasma. Together, these findings suggest that while wild-type Ass is readily transported out of brain into plasma, Dutch/Iowa mutant Ass is deficient in this clearance process, likely contributing to its robust accumulation in the cerebral vasculature. |
