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The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease

Mild cognitive impairment (MCI) is characterized by memory loss in the absence of dementia and is considered the translational stage between normal aging and early Alzheimer’s disease (AD). Patients with MCI have a greater risk of advancing to AD. Thus, identifying early markers of MCI has the poten...

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Autores principales: Scott, Xavier O., Stephens, Marisa E., Desir, Marie C., Dietrich, W. Dalton, Keane, Robert W., de Rivero Vaccari, Juan Pablo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370034/
https://www.ncbi.nlm.nih.gov/pubmed/32630059
http://dx.doi.org/10.3390/ijms21134674
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author Scott, Xavier O.
Stephens, Marisa E.
Desir, Marie C.
Dietrich, W. Dalton
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_facet Scott, Xavier O.
Stephens, Marisa E.
Desir, Marie C.
Dietrich, W. Dalton
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
author_sort Scott, Xavier O.
collection PubMed
description Mild cognitive impairment (MCI) is characterized by memory loss in the absence of dementia and is considered the translational stage between normal aging and early Alzheimer’s disease (AD). Patients with MCI have a greater risk of advancing to AD. Thus, identifying early markers of MCI has the potential to increase the therapeutic window to treat and manage the disease. Protein levels of the inflammasome signaling proteins apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and interleukin (IL)-18 were analyzed in the serum of patients with MCI, AD and healthy age-matched donors as possible biomarkers, as well as levels of soluble amyloid precursor proteins α/β (sAPP α/β) and neurofilament light (NfL). Cut-off points and positive and negative predictive values, as well as receiver operator characteristic (ROC) curves, likelihood ratios and accuracy were determined for these proteins. Although the levels of ASC were higher in MCI and AD than in age-matched controls, protein levels of ASC were higher in MCI than in AD cases. For control vs. MCI, the area under the curve (AUC) for ASC was 0.974, with a cut-off point of 264.9 pg/mL. These data were comparable to the AUC for sAPP α and β of 0.9687 and 0.9068, respectively, as well as 0.7734 for NfL. Moreover, similar results were obtained for control vs. AD and MCI vs. AD. These results indicate that ASC is a promising biomarker of MCI and AD.
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spelling pubmed-73700342020-07-21 The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease Scott, Xavier O. Stephens, Marisa E. Desir, Marie C. Dietrich, W. Dalton Keane, Robert W. de Rivero Vaccari, Juan Pablo Int J Mol Sci Article Mild cognitive impairment (MCI) is characterized by memory loss in the absence of dementia and is considered the translational stage between normal aging and early Alzheimer’s disease (AD). Patients with MCI have a greater risk of advancing to AD. Thus, identifying early markers of MCI has the potential to increase the therapeutic window to treat and manage the disease. Protein levels of the inflammasome signaling proteins apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and interleukin (IL)-18 were analyzed in the serum of patients with MCI, AD and healthy age-matched donors as possible biomarkers, as well as levels of soluble amyloid precursor proteins α/β (sAPP α/β) and neurofilament light (NfL). Cut-off points and positive and negative predictive values, as well as receiver operator characteristic (ROC) curves, likelihood ratios and accuracy were determined for these proteins. Although the levels of ASC were higher in MCI and AD than in age-matched controls, protein levels of ASC were higher in MCI than in AD cases. For control vs. MCI, the area under the curve (AUC) for ASC was 0.974, with a cut-off point of 264.9 pg/mL. These data were comparable to the AUC for sAPP α and β of 0.9687 and 0.9068, respectively, as well as 0.7734 for NfL. Moreover, similar results were obtained for control vs. AD and MCI vs. AD. These results indicate that ASC is a promising biomarker of MCI and AD. MDPI 2020-06-30 /pmc/articles/PMC7370034/ /pubmed/32630059 http://dx.doi.org/10.3390/ijms21134674 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scott, Xavier O.
Stephens, Marisa E.
Desir, Marie C.
Dietrich, W. Dalton
Keane, Robert W.
de Rivero Vaccari, Juan Pablo
The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title_full The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title_fullStr The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title_full_unstemmed The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title_short The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease
title_sort inflammasome adaptor protein asc in mild cognitive impairment and alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370034/
https://www.ncbi.nlm.nih.gov/pubmed/32630059
http://dx.doi.org/10.3390/ijms21134674
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