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Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology

Pereira, Joana B. LU ; Janelidze, Shorena LU ; Strandberg, Olof LU ; Whelan, Christopher D. ; Zetterberg, Henrik LU ; Blennow, Kaj LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2022) In Nature Aging 2(12). p.1138-1144
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... (More)

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.

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published
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in
Nature Aging
volume
2
issue
12
pages
7 pages
publisher
Springer
external identifiers
  • scopus:85142786687
  • pmid:37118533
DOI
10.1038/s43587-022-00310-z
language
English
LU publication?
yes
id
ef69e907-c26b-4ee7-9c5c-365790360540
date added to LUP
2023-01-31 14:15:32
date last changed
2024-06-26 06:07:34
@article{ef69e907-c26b-4ee7-9c5c-365790360540,
  abstract     = {{<p>The role of microglia in tau accumulation is currently unclear but could provide an important insight into the mechanisms underlying Alzheimer’s disease (AD)<sup>1</sup>. 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<sup>+</sup>), 64 with additional evidence of tau-PET pathology (A<sup>+</sup>T<sup>+</sup>) and 159 without amyloid- or tau-PET pathology (A<sup>−</sup>T<sup>−</sup>). Our results showed that increased levels of TREM2 were associated with slower amyloid accumulation in A<sup>+</sup> individuals in addition to slower tau deposition and cognitive decline in A<sup>+</sup>T<sup>+</sup> subjects. Similarly, higher levels of AXL, MERTK, GAS6, LPL, CST7 and CSF1 predicted slower tau accumulation and/or cognitive decline in the A<sup>+</sup>T<sup>+</sup> group. These findings have important implications for future therapeutic strategies aiming to boost microglial protective functions in AD.</p>}},
  author       = {{Pereira, Joana B. and Janelidze, Shorena and Strandberg, Olof and Whelan, Christopher D. and Zetterberg, Henrik and Blennow, Kaj and Palmqvist, Sebastian and Stomrud, Erik and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{1138--1144}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology}},
  url          = {{http://dx.doi.org/10.1038/s43587-022-00310-z}},
  doi          = {{10.1038/s43587-022-00310-z}},
  volume       = {{2}},
  year         = {{2022}},
}