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Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasin...

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Autores principales: Stroffolini, Giacomo, Guastamacchia, Giulia, Audagnotto, Sabrina, Atzori, Cristiana, Trunfio, Mattia, Nigra, Marco, Di Stefano, Alessandro, Di Perri, Giovanni, Calcagno, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594191/
https://www.ncbi.nlm.nih.gov/pubmed/34784880
http://dx.doi.org/10.1186/s12883-021-02468-2
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author Stroffolini, Giacomo
Guastamacchia, Giulia
Audagnotto, Sabrina
Atzori, Cristiana
Trunfio, Mattia
Nigra, Marco
Di Stefano, Alessandro
Di Perri, Giovanni
Calcagno, Andrea
author_facet Stroffolini, Giacomo
Guastamacchia, Giulia
Audagnotto, Sabrina
Atzori, Cristiana
Trunfio, Mattia
Nigra, Marco
Di Stefano, Alessandro
Di Perri, Giovanni
Calcagno, Andrea
author_sort Stroffolini, Giacomo
collection PubMed
description BACKGROUND: Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases. METHODS: We retrospectively included 13 HIV-negative patients presenting with TBM and we compared them with two control groups: one of patients with a confirmed diagnosis of AD, and one of those with syphilis where lumbar punctures excluded central nervous system involvement. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, “CSAR”), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aβ1–42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 β). RESULTS: TBM patients were 83 % male and 67 % Caucasian with a median age of 51 years (24.5–63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1–30.9 IQR), neopterin (14.3 ng/ml, 9.7–18.8) and IgG ratios (15.4, 7.9–24.9), patients showed very low levels of Aβ1–42 in their CSF (348.5 pg/mL,125-532.2), even lower compared to AD and controls [603 pg/mL (IQR 528–797) and 978 (IQR 789–1178)]. Protein 14.3.3 tested altered in 38.5 % cases. T-tau, P-tau and S100Beta were in the range of normality. Altered low level of Aβ1–42 correlated over time with classical TBM findings and altered neuromarkers. CONCLUSIONS: CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aβ1–42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-021-02468-2.
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spelling pubmed-85941912021-11-16 Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis Stroffolini, Giacomo Guastamacchia, Giulia Audagnotto, Sabrina Atzori, Cristiana Trunfio, Mattia Nigra, Marco Di Stefano, Alessandro Di Perri, Giovanni Calcagno, Andrea BMC Neurol Research BACKGROUND: Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases. METHODS: We retrospectively included 13 HIV-negative patients presenting with TBM and we compared them with two control groups: one of patients with a confirmed diagnosis of AD, and one of those with syphilis where lumbar punctures excluded central nervous system involvement. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, “CSAR”), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aβ1–42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 β). RESULTS: TBM patients were 83 % male and 67 % Caucasian with a median age of 51 years (24.5–63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1–30.9 IQR), neopterin (14.3 ng/ml, 9.7–18.8) and IgG ratios (15.4, 7.9–24.9), patients showed very low levels of Aβ1–42 in their CSF (348.5 pg/mL,125-532.2), even lower compared to AD and controls [603 pg/mL (IQR 528–797) and 978 (IQR 789–1178)]. Protein 14.3.3 tested altered in 38.5 % cases. T-tau, P-tau and S100Beta were in the range of normality. Altered low level of Aβ1–42 correlated over time with classical TBM findings and altered neuromarkers. CONCLUSIONS: CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aβ1–42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-021-02468-2. BioMed Central 2021-11-16 /pmc/articles/PMC8594191/ /pubmed/34784880 http://dx.doi.org/10.1186/s12883-021-02468-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Stroffolini, Giacomo
Guastamacchia, Giulia
Audagnotto, Sabrina
Atzori, Cristiana
Trunfio, Mattia
Nigra, Marco
Di Stefano, Alessandro
Di Perri, Giovanni
Calcagno, Andrea
Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title_full Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title_fullStr Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title_full_unstemmed Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title_short Low cerebrospinal fluid Amyloid-βeta 1–42 in patients with tuberculous meningitis
title_sort low cerebrospinal fluid amyloid-βeta 1–42 in patients with tuberculous meningitis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594191/
https://www.ncbi.nlm.nih.gov/pubmed/34784880
http://dx.doi.org/10.1186/s12883-021-02468-2
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