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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...

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Autores principales: Bivona, Giulia, Iemmolo, Matilda, Piccoli, Tommaso, Agnello, Luisa, Lo Sasso, Bruna, Ciaccio, Marcello, Ghersi, Giulio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
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.
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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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