| First Author | Sagare AP | Year | 2013 |
| Journal | Nat Commun | Volume | 4 |
| Pages | 2932 | PubMed ID | 24336108 |
| Mgi Jnum | J:221300 | Mgi Id | MGI:5638846 |
| Doi | 10.1038/ncomms3932 | Citation | Sagare AP, et al. (2013) Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun 4:2932 |
| abstractText | Pericytes are cells in the blood-brain barrier that degenerate in Alzheimer's disease (AD), a neurological disorder associated with neurovascular dysfunction, abnormal elevation of amyloid beta-peptide (Abeta), tau pathology and neuronal loss. Whether pericyte degeneration can influence AD-like neurodegeneration and contribute to disease pathogenesis remains, however, unknown. Here we show that in mice overexpressing Abeta-precursor protein, pericyte loss elevates brain Abeta40 and Abeta42 levels and accelerates amyloid angiopathy and cerebral beta-amyloidosis by diminishing clearance of soluble Abeta40 and Abeta42 from brain interstitial fluid prior to Abeta deposition. We further show that pericyte deficiency leads to the development of tau pathology and an early neuronal loss that is normally absent in Abeta-precursor protein transgenic mice, resulting in cognitive decline. Our data suggest that pericytes control multiple steps of AD-like neurodegeneration pathogenic cascade in Abeta-precursor protein-overexpressing mice. Therefore, pericytes may represent a novel therapeutic target to modify disease progression in AD. |
