Woo, MS;
Nilsson, J;
Therriault, J;
Rahmouni, N;
Brinkmalm, A;
Benedet, AL;
Ashton, NJ;
... Rosa-Neto, P; + view all
(2023)
14-3-3 ζ/δ-reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2.
Journal of Neuroinflammation
, 20
, Article 278. 10.1186/s12974-023-02962-z.
Preview |
PDF
s12974-023-02962-z.pdf - Published Version Download (1MB) | Preview |
Abstract
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 (ζ / δ) 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 ζ / δ was increased in participants with amyloid pathology at the early stages of tau aggregation before hippocampal volume loss was detectable. 14-3-3 ζ / δ 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.
| Type: | Article |
|---|---|
| Title: | 14-3-3 ζ/δ-reported early synaptic injury in Alzheimer’s disease is independently mediated by sTREM2 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12974-023-02962-z |
| Publisher version: | https://doi.org/10.1186/s12974-023-02962-z |
| Language: | English |
| Additional information: | 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/. The Creative Commons Public Domain Dedication waiver (http://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. |
| Keywords: | Alzheimer’s disease, Microglia, Neuroinflammation, Synaptic loss, sTREM2, Humans, Alzheimer Disease, Amyloid beta-Peptides, Amyloidosis, Biomarkers, Gliosis, tau Proteins, 14-3-3 Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10183688 |
Archive Staff Only
 |
View Item |
