Imperial College London
Alternate

Professor Lefkos Middleton

Faculty of Medicine, School of Public Health

Chair in Clinical Neurology
 
 
 
//

Contact

 

+44 (0)20 3311 7290l.middleton CV

 
 
//

Assistant

 

Ms Naia Headland-Vanni +44 (0)20 3311 7290

 
//

Location

 

Room 10L05 LaboratoryCharing Cross HospitalCharing Cross Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Wilson:2020:10.1002/mds.28064,
author = {Wilson, H and Pagano, G and de, Natale ER and Mansur, A and Caminiti, SP and Polychronis, S and Middleton, LT and Price, G and Schmidt, KF and Gunn, RN and Rabiner, EA and Politis, M},
doi = {10.1002/mds.28064},
journal = {Movement Disorders},
pages = {1416--1427},
title = {Mitochondrial complex 1, sigma 1, and synaptic vesicle 2A in early drug-naive Parkinson's Disease},
url = {http://dx.doi.org/10.1002/mds.28064},
volume = {35},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundDysfunction of mitochondrial energy generation may contribute to neurodegeneration, leading to synaptic loss in Parkinson's disease (PD). The objective of this study was to find crosssectional and longitudinal changes in PET markers of synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1 in drugnaive PD patients.MethodsTwelve early drugnaive PD patients and 16 healthy controls underwent a 3Tesla MRI and PET imaging to quantify volume of distribution of [11C]UCBJ, [11C]SA4503, and [18F]BCPPEF for synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1, respectively. Nine PD patients completed approximately 1year followup assessments.ResultsReduced [11C]UCBJ volume of distribution in the caudate, putamen, thalamus, brain stem, and dorsal raphe and across cortical regions was observed in drugnaive PD patients compared with healthy controls. [11C]UCBJ volume of distribution was reduced in the locus coeruleus and substantia nigra but did not reach statistical significance. No significant differences were found in [11C]SA4503 and [18F]BCPPEF volume of distribution in PD compared with healthy controls. Lower brain stem [11C]UCBJ volume of distribution correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale part III and total scores. No significant longitudinal changes were identified in PD patients at followup compared with baseline.ConclusionsOur findings represent the first in vivo evidence of mitochondrial, endoplasmic reticulum, and synaptic dysfunction in drugnaive PD patients. Synaptic dysfunction likely occurs early in disease pathophysiology and has relevance to symptomatology. Mitochondrial complex 1 and sigma 1 receptor pathology warrants further investigations in PD. Studies in larger cohorts with longer followup will determine the validity of these PET markers to track disease progression. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, In
AU  - Wilson,H
AU  - Pagano,G
AU  - de,Natale ER
AU  - Mansur,A
AU  - Caminiti,SP
AU  - Polychronis,S
AU  - Middleton,LT
AU  - Price,G
AU  - Schmidt,KF
AU  - Gunn,RN
AU  - Rabiner,EA
AU  - Politis,M
DO  - 10.1002/mds.28064
EP  - 1427
PY  - 2020///
SN  - 0885-3185
SP  - 1416
TI  - Mitochondrial complex 1, sigma 1, and synaptic vesicle 2A in early drug-naive Parkinson's Disease
T2  - Movement Disorders
UR  - http://dx.doi.org/10.1002/mds.28064
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000529275700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/full/10.1002/mds.28064
UR  - http://hdl.handle.net/10044/1/79093
VL  - 35
ER  -
Download