| First Author | Bannai T | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 2827 |
| PubMed ID | 30808940 | Mgi Jnum | J:349637 |
| Mgi Id | MGI:6304876 | Doi | 10.1038/s41598-019-39494-7 |
| Citation | Bannai T, et al. (2019) Chronic cerebral hypoperfusion shifts the equilibrium of amyloid beta oligomers to aggregation-prone species with higher molecular weight. Sci Rep 9(1):2827 |
| abstractText | Epidemiological studies have shown that atherosclerotic risk factors accelerate the pathological process underlying Alzheimer's disease (AD) via chronic cerebral hypoperfusion. In this study, we aimed to clarify the mechanisms by which cerebral hypoperfusion may exacerbate AD pathology. We applied bilateral common carotid artery stenosis (BCAS) to a mice model of AD and evaluated how the equilibrium of amyloid beta oligomers respond to hypoperfusion. BCAS accelerated amyloid beta (Abeta) convergence to the aggregation seed, facilitating the growth of Abeta plaques, but without changing the total Abeta amount in the brain. Furthermore, Abeta oligomers with high molecular weight increased in the brain of BCAS-operated mice. Considering Abeta is in an equilibrium among monomeric, oligomeric, and aggregation forms, our data suggest that cerebral hypoperfusion after BCAS shifted this equilibrium to a state where a greater number of Abeta molecules participate in Abeta assemblies to form aggregation-prone Abeta oligomers with high molecular weight. The reduced blood flow in the cerebral arteries due to BCAS attenuated the dynamics of the interstitial fluid leading to congestion, which may have facilitated Abeta aggregation. We suggest that cerebral hypoperfusion may accelerate AD by enhancing the tendency of Abeta to become aggregation-prone. |
