Pereira, Joana B;
Janelidze, Shorena;
Strandberg, Olof;
Whelan, Christopher D;
Zetterberg, Henrik;
Blennow, Kaj;
Palmqvist, Sebastian;
... Hansson, Oskar; + view all
(2022)
Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology.
Nature Aging
10.1038/s43587-022-00310-z.
(In press).
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Abstract
The role of microglia in tau accumulation is currently unclear but could provide an important insight into the mechanisms underlying Alzheimer’s disease (AD)1. Here, we measured the microglial marker soluble TREM2 and the disease-associated microglial activation stage 2 markers AXL, MERTK, GAS6, LPL, CST7, SPP1 and CSF1 in nondemented individuals from the Swedish BioFINDER-2 cohort who underwent longitudinal tau-positron emission tomography (PET), amyloid-PET and global cognitive assessment. To assess whether baseline microglial markers had an effect on AD-related changes, we studied three sub-groups of individuals: 121 with evidence of amyloid-PET pathology (A+), 64 with additional evidence of tau-PET pathology (A+T+) and 159 without amyloid- or tau-PET pathology (A−T−). Our results showed that increased levels of TREM2 were associated with slower amyloid accumulation in A+ individuals in addition to slower tau deposition and cognitive decline in A+T+ subjects. Similarly, higher levels of AXL, MERTK, GAS6, LPL, CST7 and CSF1 predicted slower tau accumulation and/or cognitive decline in the A+T+ group. These findings have important implications for future therapeutic strategies aiming to boost microglial protective functions in AD.
| Type: | Article |
|---|---|
| Title: | Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s43587-022-00310-z |
| Publisher version: | https://doi.org/10.1038/s43587-022-00310-z |
| Language: | English |
| Additional information: | © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Ageing, Alzheimer's disease, Predictive markers |
| 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/10161758 |
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