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14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2

INTRODUCTION: Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes...

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Autores principales: Woo, Marcel S., Nilsson, Johanna, Therriault, Joseph, Rahmouni, Nesrine, Brinkmalm, Ann, Benedet, Andrea L., Ashton, Nicholas J., Macedo, Arthur C., Servaes, Stijn, Wang, Yi-Ting, Tissot, Cécile, Arias, Jaime Fernandez, Hosseini, Seyyed Ali, Chamoun, Mira, Lussier, Firoza Z., Karikari, Thomas K., Stevenson, Jenna, Mayer, Christina, Ferrari-Souza, João Pedro, Kobayashi, Eliane, Massarweh, Gassan, Friese, Manuel A., Pascoal, Tharick A., Gauthier, Serge, Zetterberg, Henrik, Blennow, Kaj, Rosa-Neto, Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675887/
https://www.ncbi.nlm.nih.gov/pubmed/38001539
http://dx.doi.org/10.1186/s12974-023-02962-z
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author Woo, Marcel S.
Nilsson, Johanna
Therriault, Joseph
Rahmouni, Nesrine
Brinkmalm, Ann
Benedet, Andrea L.
Ashton, Nicholas J.
Macedo, Arthur C.
Servaes, Stijn
Wang, Yi-Ting
Tissot, Cécile
Arias, Jaime Fernandez
Hosseini, Seyyed Ali
Chamoun, Mira
Lussier, Firoza Z.
Karikari, Thomas K.
Stevenson, Jenna
Mayer, Christina
Ferrari-Souza, João Pedro
Kobayashi, Eliane
Massarweh, Gassan
Friese, Manuel A.
Pascoal, Tharick A.
Gauthier, Serge
Zetterberg, Henrik
Blennow, Kaj
Rosa-Neto, Pedro
author_facet Woo, Marcel S.
Nilsson, Johanna
Therriault, Joseph
Rahmouni, Nesrine
Brinkmalm, Ann
Benedet, Andrea L.
Ashton, Nicholas J.
Macedo, Arthur C.
Servaes, Stijn
Wang, Yi-Ting
Tissot, Cécile
Arias, Jaime Fernandez
Hosseini, Seyyed Ali
Chamoun, Mira
Lussier, Firoza Z.
Karikari, Thomas K.
Stevenson, Jenna
Mayer, Christina
Ferrari-Souza, João Pedro
Kobayashi, Eliane
Massarweh, Gassan
Friese, Manuel A.
Pascoal, Tharick A.
Gauthier, Serge
Zetterberg, Henrik
Blennow, Kaj
Rosa-Neto, Pedro
author_sort Woo, Marcel S.
collection PubMed
description INTRODUCTION: Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes synaptic cleavage before tau aggregation appears. METHODS: We investigated 104 participants across the AD continuum by measuring 14-3-3 zeta/delta ([Formula: see text] ) as a cerebrospinal fluid biomarker for synaptic degradation, and fluid and imaging biomarkers of tau, amyloidosis, astrogliosis, neurodegeneration, and inflammation. We performed correlation analyses in cognitively unimpaired and impaired participants and used structural equation models to estimate the impact of microglia activation on synaptic injury in different disease stages. RESULTS: 14-3-3 [Formula: see text] was increased in participants with amyloid pathology at the early stages of tau aggregation before hippocampal volume loss was detectable. 14-3-3 [Formula: see text] correlated with amyloidosis and tau load in all participants but only with biomarkers of neurodegeneration and memory deficits in cognitively unimpaired participants. This early synaptic damage was independently mediated by sTREM2. At later disease stages, tau and astrogliosis additionally mediated synaptic loss. CONCLUSIONS: Our results advertise that sTREM2 is mediating synaptic injury at the early stages of tau accumulation, underlining the importance of microglia activation for AD disease propagation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02962-z.
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spelling pubmed-106758872023-11-24 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2 Woo, Marcel S. Nilsson, Johanna Therriault, Joseph Rahmouni, Nesrine Brinkmalm, Ann Benedet, Andrea L. Ashton, Nicholas J. Macedo, Arthur C. Servaes, Stijn Wang, Yi-Ting Tissot, Cécile Arias, Jaime Fernandez Hosseini, Seyyed Ali Chamoun, Mira Lussier, Firoza Z. Karikari, Thomas K. Stevenson, Jenna Mayer, Christina Ferrari-Souza, João Pedro Kobayashi, Eliane Massarweh, Gassan Friese, Manuel A. Pascoal, Tharick A. Gauthier, Serge Zetterberg, Henrik Blennow, Kaj Rosa-Neto, Pedro J Neuroinflammation Research INTRODUCTION: Synaptic loss is closely associated with tau aggregation and microglia activation in later stages of Alzheimer’s disease (AD). However, synaptic damage happens early in AD at the very early stages of tau accumulation. It remains unclear whether microglia activation independently causes synaptic cleavage before tau aggregation appears. METHODS: We investigated 104 participants across the AD continuum by measuring 14-3-3 zeta/delta ([Formula: see text] ) as a cerebrospinal fluid biomarker for synaptic degradation, and fluid and imaging biomarkers of tau, amyloidosis, astrogliosis, neurodegeneration, and inflammation. We performed correlation analyses in cognitively unimpaired and impaired participants and used structural equation models to estimate the impact of microglia activation on synaptic injury in different disease stages. RESULTS: 14-3-3 [Formula: see text] was increased in participants with amyloid pathology at the early stages of tau aggregation before hippocampal volume loss was detectable. 14-3-3 [Formula: see text] correlated with amyloidosis and tau load in all participants but only with biomarkers of neurodegeneration and memory deficits in cognitively unimpaired participants. This early synaptic damage was independently mediated by sTREM2. At later disease stages, tau and astrogliosis additionally mediated synaptic loss. CONCLUSIONS: Our results advertise that sTREM2 is mediating synaptic injury at the early stages of tau accumulation, underlining the importance of microglia activation for AD disease propagation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02962-z. BioMed Central 2023-11-24 /pmc/articles/PMC10675887/ /pubmed/38001539 http://dx.doi.org/10.1186/s12974-023-02962-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Woo, Marcel S.
Nilsson, Johanna
Therriault, Joseph
Rahmouni, Nesrine
Brinkmalm, Ann
Benedet, Andrea L.
Ashton, Nicholas J.
Macedo, Arthur C.
Servaes, Stijn
Wang, Yi-Ting
Tissot, Cécile
Arias, Jaime Fernandez
Hosseini, Seyyed Ali
Chamoun, Mira
Lussier, Firoza Z.
Karikari, Thomas K.
Stevenson, Jenna
Mayer, Christina
Ferrari-Souza, João Pedro
Kobayashi, Eliane
Massarweh, Gassan
Friese, Manuel A.
Pascoal, Tharick A.
Gauthier, Serge
Zetterberg, Henrik
Blennow, Kaj
Rosa-Neto, Pedro
14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title_full 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title_fullStr 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title_full_unstemmed 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title_short 14-3-3 [Formula: see text] -reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2
title_sort 14-3-3 [formula: see text] -reported early synaptic injury in alzheimer’s disease is independently mediated by strem2
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675887/
https://www.ncbi.nlm.nih.gov/pubmed/38001539
http://dx.doi.org/10.1186/s12974-023-02962-z
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