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High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia
Alzheimer’s disease (AD) is the most common form of cognitive decline worldwide, occurring in about 10% of people older than 65 years. The well-known hallmarks of AD are extracellular aggregates of amyloid β (Aβ) and intracellular neurofibrillary tangles (NFTs) of tau protein. The evidence that Aβ o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571188/ https://www.ncbi.nlm.nih.gov/pubmed/36233371 http://dx.doi.org/10.3390/jcm11195498 |
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author | Bivona, Giulia Iemmolo, Matilda Piccoli, Tommaso Agnello, Luisa Lo Sasso, Bruna Ciaccio, Marcello Ghersi, Giulio |
author_facet | Bivona, Giulia Iemmolo, Matilda Piccoli, Tommaso Agnello, Luisa Lo Sasso, Bruna Ciaccio, Marcello Ghersi, Giulio |
author_sort | Bivona, Giulia |
collection | PubMed |
description | Alzheimer’s disease (AD) is the most common form of cognitive decline worldwide, occurring in about 10% of people older than 65 years. The well-known hallmarks of AD are extracellular aggregates of amyloid β (Aβ) and intracellular neurofibrillary tangles (NFTs) of tau protein. The evidence that Aβ overproduction leads to AD has paved the way for the AD pathogenesis amyloid cascade hypothesis, which proposes that the neuronal damage is sustained by Aβ overproduction. Consistently, AD cerebrospinal fluid (CSF) biomarkers used in clinical practice, including Aβ 1–42, Aβ 1–40, Aβ 42/40 ratio, and pTau, are related to the amyloid hypothesis. Recently, it was suggested that the Aβ deposition cascade cannot fully disclose AD pathogenesis, with other putative players being involved in the pathophysiology of the disease. Among all, one of the most studied factors is inflammation in the brain. Hence, biomarkers of inflammation and microglia activation have also been proposed to identify AD. Among them, CX3 chemokine ligand 1 (CX3CL1) has taken center stage. This transmembrane protein, also known as fractalkine (FKN), is normally expressed in neurons, featuring an N-terminal chemokine domain and an extended mucin-like stalk, following a short intra-cytoplasmatic domain. The molecule exists in both membrane-bound and soluble forms. It is accepted that the soluble and membrane-bound forms of FKN evoke differential signaling within the CNS. Given the link between CX3XL1 and microglial activation, it has been suggested that CX3CL1 signaling disruption could play a part in the pathogenesis of AD. Furthermore, a role for chemokine as a biomarker has been proposed. However, the findings collected are controversial. The current study aimed to describe the cerebrospinal fluid (CSF) levels of CX3XL1 and classical biomarkers in AD patients. |
format | Online Article Text |
id | pubmed-9571188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95711882022-10-17 High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia Bivona, Giulia Iemmolo, Matilda Piccoli, Tommaso Agnello, Luisa Lo Sasso, Bruna Ciaccio, Marcello Ghersi, Giulio J Clin Med Article Alzheimer’s disease (AD) is the most common form of cognitive decline worldwide, occurring in about 10% of people older than 65 years. The well-known hallmarks of AD are extracellular aggregates of amyloid β (Aβ) and intracellular neurofibrillary tangles (NFTs) of tau protein. The evidence that Aβ overproduction leads to AD has paved the way for the AD pathogenesis amyloid cascade hypothesis, which proposes that the neuronal damage is sustained by Aβ overproduction. Consistently, AD cerebrospinal fluid (CSF) biomarkers used in clinical practice, including Aβ 1–42, Aβ 1–40, Aβ 42/40 ratio, and pTau, are related to the amyloid hypothesis. Recently, it was suggested that the Aβ deposition cascade cannot fully disclose AD pathogenesis, with other putative players being involved in the pathophysiology of the disease. Among all, one of the most studied factors is inflammation in the brain. Hence, biomarkers of inflammation and microglia activation have also been proposed to identify AD. Among them, CX3 chemokine ligand 1 (CX3CL1) has taken center stage. This transmembrane protein, also known as fractalkine (FKN), is normally expressed in neurons, featuring an N-terminal chemokine domain and an extended mucin-like stalk, following a short intra-cytoplasmatic domain. The molecule exists in both membrane-bound and soluble forms. It is accepted that the soluble and membrane-bound forms of FKN evoke differential signaling within the CNS. Given the link between CX3XL1 and microglial activation, it has been suggested that CX3CL1 signaling disruption could play a part in the pathogenesis of AD. Furthermore, a role for chemokine as a biomarker has been proposed. However, the findings collected are controversial. The current study aimed to describe the cerebrospinal fluid (CSF) levels of CX3XL1 and classical biomarkers in AD patients. MDPI 2022-09-20 /pmc/articles/PMC9571188/ /pubmed/36233371 http://dx.doi.org/10.3390/jcm11195498 Text en © 2022 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 Bivona, Giulia Iemmolo, Matilda Piccoli, Tommaso Agnello, Luisa Lo Sasso, Bruna Ciaccio, Marcello Ghersi, Giulio High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title | High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title_full | High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title_fullStr | High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title_full_unstemmed | High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title_short | High Cerebrospinal Fluid CX3CL1 Levels in Alzheimer’s Disease Patients but Not in Non-Alzheimer’s Disease Dementia |
title_sort | high cerebrospinal fluid cx3cl1 levels in alzheimer’s disease patients but not in non-alzheimer’s disease dementia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571188/ https://www.ncbi.nlm.nih.gov/pubmed/36233371 http://dx.doi.org/10.3390/jcm11195498 |
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