Pericyte loss influences Alzheimer-like neurodegeneration in mice (Nat Commun. 2013 Dec 13;4:2932.)

報告日期: 2014/05/16
報告時間: 4:00/4:50
報告學生: 蔡昇峰
講評老師: 許鍾瑜
附件下載: 下載[1409-1396957791-1.pdf] 

 Pericyte loss influences Alzheimer-like neurodegeneration in mice

Abhay P. Sagare, et al. 2013. Nat Commun. 2013 Dec 13;4:2932

Speaker: Sheng-Feng Tsai

Commentator: Dr. Jung-Yu C. Hsu

Date: 05/16, 2014

Alzheimer’s disease, a neurodegenerative disorder associated with abnormal elevation of amyloid β-peptide, tau pathology and neuronal loss, is a consequence of heterogeneous and complex interactions of age-related neurodegeneration and vascular-associated pathologies. In the cerebrovascular system, pericytes regulate blood-brain barrier formation and maintenance, capillary blood flow, and clearance of toxic cellular byproducts necessary for normal functioning of the central nervous system. However, whether pericyte loss can influence the natural course of Alzheimer’s disease-like neurodegeneration and contribute to disease pathogenesis remains unknown. To address this question, the authors crossed transgenic mice overexpressing the Swedish mutation of human Aβ-precursor protein (APPsw/0) with pericyte-deficient platelet-derived growth factor receptor-β (Pdgfrβ/) mice. The results revealed that in mice overexpressing Aβ-precursor protein, pericyte loss elevates brain Aβ40 and Aβ42 levels and accelerates amyloid angiopathy and cerebral β-amyloidosis by diminishing clearance of soluble Aβ40 and Aβ42 from brain interstitial fluid prior to Aβ deposition. The authors further showed that pericyte deficiency leads to the development of tau pathology and an early neuronal loss that is normally absent in Aβ-precursor protein transgenic mice, resulting in cognitive decline. Thus, pericyte loss has an effect on multiple steps of Alzheimer’s disease-like neurodegeneration pathogenic cascade in APPsw/0 mice suggesting that pericytes may represent a novel therapeutic target to modify disease progression in Alzheimer’s disease.