Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785149868775309312 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10675887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT woomarcels 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT nilssonjohanna 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT therriaultjoseph 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT rahmouninesrine 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT brinkmalmann 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT benedetandreal 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT ashtonnicholasj 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT macedoarthurc 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT servaesstijn 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT wangyiting 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT tissotcecile 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT ariasjaimefernandez 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT hosseiniseyyedali 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT chamounmira 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT lussierfirozaz 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT karikarithomask 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT stevensonjenna 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT mayerchristina 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT ferrarisouzajoaopedro 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT kobayashieliane 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT massarwehgassan 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT friesemanuela 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT pascoaltharicka 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT gauthierserge 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT zetterberghenrik 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT blennowkaj 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 AT rosanetopedro 1433formulaseetextreportedearlysynapticinjuryinalzheimersdiseaseisindependentlymediatedbystrem2 |