Imperial College London
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ProfessorAnneLingford-Hughes

Faculty of Medicine, Department of Brain Sciences

Chair in Addiction Biology
 
 
 
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Contact

 

+44 (0)20 7594 8682anne.lingford-hughes Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Venkataraman:2021:10.1101/2021.11.23.21266746,
author = {Venkataraman, A and Bishop, C and Mansur, A and Rizzo, G and Lewis, Y and Kocagoncu, E and Lingford-Hughes, A and Huiban, M and Passchier, J and Rowe, JB and Tsukada, H and Brooks, DJ and Martarello, L and Comley, RA and Chen, L and Hargreaves, R and Schwarz, AJ and Gunn, RN and Rabiner, E and Matthews, PM},
doi = {10.1101/2021.11.23.21266746},
publisher = {Cold Spring Harbor Laboratory},
title = {Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease},
url = {http://dx.doi.org/10.1101/2021.11.23.21266746},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - Background Synaptic loss and neurite dystrophy are early events in Alzheimer’s Disease (AD). We aimed to characterise early synaptic microstructural changes in vivo.Methods MRI neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI) were used to image cortical microstructure in both sporadic, late onset, amyloid PET positive AD patients and healthy controls (total n = 28). We derived NODDI measures of grey matter extracellular free water (FISO), neurite density (NDI) and orientation dispersion (ODI), which provides an index of neurite branching and orientation, as well as more conventional DTI measures of fractional anisotropy (FA), mean/axial/radial diffusivity (MD, AD, RD, respectively). We also performed [11C]UCB-J PET, which provides a specific measure of the density of pre-synaptic vesicular protein SV2A. Both sets of measures were compared to regional brain volumes.Results The AD patients showed expected relative decreases in regional brain volumes (range, -6 to - 23%) and regional [11C]UCB-J densities (range, -2 to -25%). Differences between AD and controls were greatest in the hippocampus. NODDI microstructural measures showed greater FISO (range, +26 to +44%) in AD, with little difference in NDI (range, -1 to +7%) and mild focal changes in ODI (range, -4 to +3%). Regionally greater FISO and lower [11C]UCB-J binding were correlated across grey matter in patients (most strongly in the caudate, r2 = 0.37, p = 0.001). FISO and DTI RD were strongly positively associated, particularly in the hippocampus (r2 = 0.98, p < 7.4 × 10−9). After 12-18 months we found a 5% increase in FISO in the temporal lobe, but little change across all ROIs in NDI and ODI. An exploratory analysis showed higher parietal lobe FISO was associated with lower language scores in people with AD.Conclusions We interpreted the increased extracellular free water as a possible consequence of glial activation. The dynamic range of disease
AU  - Venkataraman,A
AU  - Bishop,C
AU  - Mansur,A
AU  - Rizzo,G
AU  - Lewis,Y
AU  - Kocagoncu,E
AU  - Lingford-Hughes,A
AU  - Huiban,M
AU  - Passchier,J
AU  - Rowe,JB
AU  - Tsukada,H
AU  - Brooks,DJ
AU  - Martarello,L
AU  - Comley,RA
AU  - Chen,L
AU  - Hargreaves,R
AU  - Schwarz,AJ
AU  - Gunn,RN
AU  - Rabiner,E
AU  - Matthews,PM
DO  - 10.1101/2021.11.23.21266746
PB  - Cold Spring Harbor Laboratory
PY  - 2021///
TI  - Imaging synaptic microstructure and synaptic loss in vivo in early Alzheimer’s Disease
UR  - http://dx.doi.org/10.1101/2021.11.23.21266746
UR  - https://www.medrxiv.org/content/10.1101/2021.11.23.21266746v1
UR  - http://hdl.handle.net/10044/1/93156
ER  -
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