Imperial College London
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DrChristopherButler

Faculty of Medicine, School of Public Health

Reader in Chronic and Complex Diseases
 
 
 
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Contact

 

christopher.butler Website

 
 
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Location

 

Department of Brain SciencesSir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Altmann:2020:braincomms/fcaa122,
author = {Altmann, A and Cash, DM and Bocchetta, M and Heller, C and Reynolds, R and Moore, K and Convery, RS and Thomas, DL and van, Swieten JC and Moreno, F and Sanchez-Valle, R and Borroni, B and Laforce, R and Masellis, M and Tartaglia, MC and Graff, C and Galimberti, D and Rowe, JB and Finger, E and Synofzik, M and Vandenberghe, R and de, Mendonca A and Tagliavini, F and Santana, I and Ducharme, S and Butler, CR and Gerhard, A and Levin, J and Danek, A and Frisoni, G and Ghidoni, R and Sorbi, S and Otto, M and Ryten, M and Rohrer, JD},
doi = {braincomms/fcaa122},
journal = {Brain Communications},
pages = {1--13},
title = {Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia},
url = {http://dx.doi.org/10.1093/braincomms/fcaa122},
volume = {2},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Frontotemporal dementia is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of frontotemporal dementia, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work, we combined gene expression data for 16 772 genes from the Allen Institute for Brain Science atlas with brain maps of grey matter atrophy in symptomatic C9orf72, GRN and MAPT mutation carriers obtained from the Genetic Frontotemporal dementia Initiative study. No significant association was seen between C9orf72, GRN and MAPT expression and the atrophy patterns in the respective genetic groups. After adjusting for spatial autocorrelation, between 1000 and 5000 genes showed a negative or positive association with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2, SSBP3 and GPR158 (negative association in C9Orf72, GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9Orf72, GRN and MAPT respectively). An overrepresentation analysis identified a negative association with genes involved in mitochondrial function, and a positive association with genes involved in vascular and glial cell function in each of the genetic groups. A set of 423 and 700 genes showed significant positive and negative association, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in frontotemporal dementia than previously assumed, and in the case of the positively associated cell marker genes, potential
AU  - Altmann,A
AU  - Cash,DM
AU  - Bocchetta,M
AU  - Heller,C
AU  - Reynolds,R
AU  - Moore,K
AU  - Convery,RS
AU  - Thomas,DL
AU  - van,Swieten JC
AU  - Moreno,F
AU  - Sanchez-Valle,R
AU  - Borroni,B
AU  - Laforce,R
AU  - Masellis,M
AU  - Tartaglia,MC
AU  - Graff,C
AU  - Galimberti,D
AU  - Rowe,JB
AU  - Finger,E
AU  - Synofzik,M
AU  - Vandenberghe,R
AU  - de,Mendonca A
AU  - Tagliavini,F
AU  - Santana,I
AU  - Ducharme,S
AU  - Butler,CR
AU  - Gerhard,A
AU  - Levin,J
AU  - Danek,A
AU  - Frisoni,G
AU  - Ghidoni,R
AU  - Sorbi,S
AU  - Otto,M
AU  - Ryten,M
AU  - Rohrer,JD
DO  - braincomms/fcaa122
EP  - 13
PY  - 2020///
SN  - 2632-1297
SP  - 1
TI  - Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia
T2  - Brain Communications
UR  - http://dx.doi.org/10.1093/braincomms/fcaa122
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000639431800063&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/braincomms/article/2/2/fcaa122/5894479
UR  - http://hdl.handle.net/10044/1/91194
VL  - 2
ER  -
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