Imperial College London
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ProfessorRichardNicholas

Faculty of Medicine, Department of Brain Sciences

Professor of Practice (Neurology)
 
 
 
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r.nicholas

 
 
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Location

 

12L12CLab BlockCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Magliozzi:2021:10.1002/acn3.51298,
author = {Magliozzi, R and Pitteri, M and Ziccardi, S and Pisani, AI and Montibeller, L and Marastoni, D and Rossi, S and Mazziotti, V and Guandalini, M and Dapor, C and Schiavi, G and Tamanti, A and Nicholas, R and Reynolds, R and Calabrese, M},
doi = {10.1002/acn3.51298},
journal = {Annals of Clinical and Translational Neurology},
pages = {534--547},
title = {CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis},
url = {http://dx.doi.org/10.1002/acn3.51298},
volume = {8},
year = {2021}
}
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TY  - JOUR
AB  - INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5
AU  - Magliozzi,R
AU  - Pitteri,M
AU  - Ziccardi,S
AU  - Pisani,AI
AU  - Montibeller,L
AU  - Marastoni,D
AU  - Rossi,S
AU  - Mazziotti,V
AU  - Guandalini,M
AU  - Dapor,C
AU  - Schiavi,G
AU  - Tamanti,A
AU  - Nicholas,R
AU  - Reynolds,R
AU  - Calabrese,M
DO  - 10.1002/acn3.51298
EP  - 547
PY  - 2021///
SN  - 2328-9503
SP  - 534
TI  - CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis
T2  - Annals of Clinical and Translational Neurology
UR  - http://dx.doi.org/10.1002/acn3.51298
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33484486
UR  - https://onlinelibrary.wiley.com/doi/10.1002/acn3.51298
UR  - http://hdl.handle.net/10044/1/85724
VL  - 8
ER  -
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