Imperial College London
Portrait Picture

ProfessorMagdalenaSastre

Faculty of Medicine, Department of Brain Sciences

Professor in Molecular Neuroscience
 
 
 
//

Contact

 

+44 (0)20 7594 6673m.sastre

 
 
//

Location

 

406Burlington DanesHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Ries:2021:brain/awab050,
author = {Ries, M and Watts, H and Mota, B and Yanez, Lopez M and Donat, C and Baxan, N and Pickering, J and Chau, TSZ and Semmler, A and Gurung, B and Aleksynas, R and Abelleira, Hervas L and Iqbal, S and Romero-Molina, C and Hernandez, Mir G and d'Amati, A and Reutelingsperger, C and Goldfinger, M and Gentleman, S and Van, Leuven F and Solito, E and Sastre, M},
doi = {brain/awab050},
journal = {Brain: a journal of neurology},
pages = {1526--1541},
title = {Annexin-A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology},
url = {http://dx.doi.org/10.1093/brain/awab050},
volume = {144},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Alzheimer’s   disease   (AD),   characterized   by   brain   deposits   of amyloid-β(Aβ)   plaques   and neurofibrillary  tangles,  is  also  linked  to  neurovascular  dysfunction  and  blood-brain  barrier  (BBB) breakdown,  affecting  the  passage  of  substances  into  and  out  of  the  brain.  We  hypothesized  that treatment of neurovascular alterations could be beneficial in AD. Annexin A1 (ANXA1) is a mediator of glucocorticoids anti-inflammatory action that can suppress microglial activation and reduce BBB leakage.  We  have  reported  recently  that  treatment  with  recombinant  human  ANXA1  (hrANXA1) 2reduced Aβ levels by increased degradation in neuroblastoma cells and phagocytosis by microglia. Here, we show the beneficial effects of hrANXA1 in vivo by restoring efficient BBB function and decreasing Aβ and tau pathology in 5xFAD mice and Tau-P301L mice. We demonstrate that young 5xFAD  mice  already  suffer  cerebrovascular  damage,  while  acute  pre-administration  of  hrANXA1 rescued the vascular defects. Interestingly, the ameliorated BBB permeability in young 5xFAD mice by hrANXA1 correlated with reduced brain A load, due to increased clearance and degradation of Aβ by the insulin degrading enzyme (IDE).  The systemic anti-inflammatory properties of hrANXA1 were also observed in 5XFAD mice, increasing IL-10 and reducing TNF-α expression. Additionally, the prolonged treatment with hrANXA1 reduced the memory deficits and increased synaptic density in  young  5xFAD  mice.  Similarly,  in  Tau-P301L  mice,  acute  hrANXA1  administration  restored vascular  architecture  integrity,  affecting  the  distribution  of  tight  junctions,  and  reduced  tau phosphorylation. The combined data support the hypothesis that the BBB breakdown early in AD can be restored by hrANXA1 as a potential therapeutic approach.
AU  - Ries,M
AU  - Watts,H
AU  - Mota,B
AU  - Yanez,Lopez M
AU  - Donat,C
AU  - Baxan,N
AU  - Pickering,J
AU  - Chau,TSZ
AU  - Semmler,A
AU  - Gurung,B
AU  - Aleksynas,R
AU  - Abelleira,Hervas L
AU  - Iqbal,S
AU  - Romero-Molina,C
AU  - Hernandez,Mir G
AU  - d'Amati,A
AU  - Reutelingsperger,C
AU  - Goldfinger,M
AU  - Gentleman,S
AU  - Van,Leuven F
AU  - Solito,E
AU  - Sastre,M
DO  - brain/awab050
EP  - 1541
PY  - 2021///
SN  - 0006-8950
SP  - 1526
TI  - Annexin-A1 restores cerebrovascular integrity concomitant with reduced amyloid-β and tau pathology
T2  - Brain: a journal of neurology
UR  - http://dx.doi.org/10.1093/brain/awab050
UR  - http://hdl.handle.net/10044/1/86223
VL  - 144
ER  -
Download