Autor: |
Siqi Chen, Daji Guo, Yuanyuan Zhu, Songhua Xiao, Jiatian Xie, Zhan Zhang, Yu Hu, Jialin Huang, Xueying Ma, Zhiyuan Ning, Lin Cao, Jinping Cheng, Yamei Tang |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-14 (2024) |
Druh dokumentu: |
article |
ISSN: |
1758-9193 |
DOI: |
10.1186/s13195-024-01423-w |
Popis: |
Abstract Background Although abnormal accumulation of amyloid beta (Aβ) protein is thought to be the main cause of Alzheimer’s disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid β induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aβ deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. Methods Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aβ oligomer stereotactic injection model was established to explain the relationship between Aβ and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. Results Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aβ-injected model, suggesting a direct relationship between Aβ and vascular dysfunction. Pericytes showed impaired features including low PDGFRβ expression and increased pro-inflammatory chemokines secretion under the administration of Aβ in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. Conclusions Our results provide new insights into the pathogenic mechanism underlying Aβ-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD. |
Databáze: |
Directory of Open Access Journals |
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