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The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database

Alzheimer’s disease (AD) and the associated neurodegenerative dementia have become of increasing concern in healthcare. The tau protein has been considered a key hallmark of progressive neurodegeneration. In this paper, a large-scale analysis of five datasets (more than 2500 people) from the Global...

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Autores principales: Eckhoff, Kyle, Morris, Robert, Zuluaga, Valeria, Polsky, Rebecca, Cheng, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301769/
https://www.ncbi.nlm.nih.gov/pubmed/34209512
http://dx.doi.org/10.3390/brainsci11070861
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author Eckhoff, Kyle
Morris, Robert
Zuluaga, Valeria
Polsky, Rebecca
Cheng, Feng
author_facet Eckhoff, Kyle
Morris, Robert
Zuluaga, Valeria
Polsky, Rebecca
Cheng, Feng
author_sort Eckhoff, Kyle
collection PubMed
description Alzheimer’s disease (AD) and the associated neurodegenerative dementia have become of increasing concern in healthcare. The tau protein has been considered a key hallmark of progressive neurodegeneration. In this paper, a large-scale analysis of five datasets (more than 2500 people) from the Global Alzheimer’s Association Interactive Network (GAAIN) databases was performed to investigate the association between the level of tau protein, including total tau and phosphorylated tau (p-tau), in cerebrospinal fluid (CSF) and cognitive status. Statistically significant (or marginally significant) high total tau or p-tau concentrations in CSF were observed in dementia patients compared with healthy people in all datasets. There is also a statistically significant (or marginally significant) negative correlation between p-tau concentrations in CSF and Folstein Mini-Mental State Examination (MMSE) scores. In addition, transcriptomic data derived from mouse microglial cells showed multiple genes upregulated in Toll-like receptor signaling and Alzheimer’s disease pathways, including TNF, TLR2, IL-1β, and COX subunits, suggesting that the mechanism of action that relates p-tau and MMSE scores may be through overactivation of pro-inflammatory microglial activity by Aβ peptides, TNF-mediated hyperphosphorylation of tau, and the infectious spread of pathological tau across healthy neurons. Our results not only confirmed the association between tau protein level and cognitive status in a large population but also provided useful information for the understanding of the role of tau in neurodegeneration and the development of dementia.
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spelling pubmed-83017692021-07-24 The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database Eckhoff, Kyle Morris, Robert Zuluaga, Valeria Polsky, Rebecca Cheng, Feng Brain Sci Article Alzheimer’s disease (AD) and the associated neurodegenerative dementia have become of increasing concern in healthcare. The tau protein has been considered a key hallmark of progressive neurodegeneration. In this paper, a large-scale analysis of five datasets (more than 2500 people) from the Global Alzheimer’s Association Interactive Network (GAAIN) databases was performed to investigate the association between the level of tau protein, including total tau and phosphorylated tau (p-tau), in cerebrospinal fluid (CSF) and cognitive status. Statistically significant (or marginally significant) high total tau or p-tau concentrations in CSF were observed in dementia patients compared with healthy people in all datasets. There is also a statistically significant (or marginally significant) negative correlation between p-tau concentrations in CSF and Folstein Mini-Mental State Examination (MMSE) scores. In addition, transcriptomic data derived from mouse microglial cells showed multiple genes upregulated in Toll-like receptor signaling and Alzheimer’s disease pathways, including TNF, TLR2, IL-1β, and COX subunits, suggesting that the mechanism of action that relates p-tau and MMSE scores may be through overactivation of pro-inflammatory microglial activity by Aβ peptides, TNF-mediated hyperphosphorylation of tau, and the infectious spread of pathological tau across healthy neurons. Our results not only confirmed the association between tau protein level and cognitive status in a large population but also provided useful information for the understanding of the role of tau in neurodegeneration and the development of dementia. MDPI 2021-06-29 /pmc/articles/PMC8301769/ /pubmed/34209512 http://dx.doi.org/10.3390/brainsci11070861 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eckhoff, Kyle
Morris, Robert
Zuluaga, Valeria
Polsky, Rebecca
Cheng, Feng
The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title_full The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title_fullStr The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title_full_unstemmed The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title_short The Association between Tau Protein Level in Cerebrospinal Fluid and Cognitive Status: A Large-Scale Analysis of GAAIN Database
title_sort association between tau protein level in cerebrospinal fluid and cognitive status: a large-scale analysis of gaain database
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301769/
https://www.ncbi.nlm.nih.gov/pubmed/34209512
http://dx.doi.org/10.3390/brainsci11070861
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