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CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders

β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1–42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involv...

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Autores principales: Mattsson, N, Insel, P, Nosheny, R, Zetterberg, H, Trojanowski, J Q, Shaw, L M, Tosun, D, Weiner, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756294/
https://www.ncbi.nlm.nih.gov/pubmed/23962923
http://dx.doi.org/10.1038/tp.2013.69
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author Mattsson, N
Insel, P
Nosheny, R
Zetterberg, H
Trojanowski, J Q
Shaw, L M
Tosun, D
Weiner, M
author_facet Mattsson, N
Insel, P
Nosheny, R
Zetterberg, H
Trojanowski, J Q
Shaw, L M
Tosun, D
Weiner, M
author_sort Mattsson, N
collection PubMed
description β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1–42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2–4 years). There was an overall reduction in Aβ42 from a mean concentration of 211–195 pg ml(−1) after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques.
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spelling pubmed-37562942013-08-29 CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders Mattsson, N Insel, P Nosheny, R Zetterberg, H Trojanowski, J Q Shaw, L M Tosun, D Weiner, M Transl Psychiatry Original Article β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1–42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2–4 years). There was an overall reduction in Aβ42 from a mean concentration of 211–195 pg ml(−1) after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques. Nature Publishing Group 2013-08 2013-08-20 /pmc/articles/PMC3756294/ /pubmed/23962923 http://dx.doi.org/10.1038/tp.2013.69 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Mattsson, N
Insel, P
Nosheny, R
Zetterberg, H
Trojanowski, J Q
Shaw, L M
Tosun, D
Weiner, M
CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title_full CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title_fullStr CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title_full_unstemmed CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title_short CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders
title_sort csf protein biomarkers predicting longitudinal reduction of csf β-amyloid42 in cognitively healthy elders
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756294/
https://www.ncbi.nlm.nih.gov/pubmed/23962923
http://dx.doi.org/10.1038/tp.2013.69
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