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Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.

Publication ,  Journal Article
Franzmeier, N; Suárez-Calvet, M; Frontzkowski, L; Moore, A; Hohman, TJ; Morenas-Rodriguez, E; Nuscher, B; Shaw, L; Trojanowski, JQ; Dichgans, M ...
Published in: Mol Neurodegener
October 8, 2020

BACKGROUND: The Apolipoprotein E ε4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. METHODS: We included 708 subjects ranging from cognitively normal (CN, n = 221) to mild cognitive impairment (MCI, n = 414) and AD dementia (n = 73) from the Alzheimer's disease Neuroimaging Initiative. We used linear regression to test the interaction between ApoE4-carriage by CSF-assessed sTREM2 levels as a predictor of longitudinally assessed cognitive decline and MRI-assessed changes in hippocampal volume changes (mean follow-up of 4 years, range of 1.7-7 years). RESULTS: Across the entire sample, we found that higher CSF sTREM2 at baseline was associated with attenuated effects of ApoE4-carriage (i.e. sTREM2 x ApoE4 interaction) on longitudinal global cognitive (p = 0.001, Cohen's f2 = 0.137) and memory decline (p = 0.006, Cohen's f2 = 0.104) as well as longitudinally assessed hippocampal atrophy (p = 0.046, Cohen's f2 = 0.089), independent of CSF markers of primary AD pathology (i.e. Aβ1-42, p-tau181). While overall effects of sTREM2 were small, exploratory subanalyses stratified by diagnostic groups showed that beneficial effects of sTREM2 were pronounced in the MCI group. CONCLUSION: Our results suggest that a higher CSF sTREM2 levels are associated with attenuated ApoE4-related risk for future cognitive decline and AD-typical neurodegeneration. These findings provide further evidence that TREM2 may be protective against the development of AD.

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Published In

Mol Neurodegener

DOI

EISSN

1750-1326

Publication Date

October 8, 2020

Volume

15

Issue

1

Start / End Page

57

Location

England

Related Subject Headings

  • Receptors, Immunologic
  • Neurology & Neurosurgery
  • Nerve Degeneration
  • Membrane Glycoproteins
  • Male
  • Humans
  • Genetic Predisposition to Disease
  • Female
  • Cognitive Dysfunction
  • Apolipoprotein E4
 

Citation

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Franzmeier, N., Suárez-Calvet, M., Frontzkowski, L., Moore, A., Hohman, T. J., Morenas-Rodriguez, E., … Alzheimer’s Disease Neuroimaging Initiative (ADNI), . (2020). Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration. Mol Neurodegener, 15(1), 57. https://doi.org/10.1186/s13024-020-00407-2
Franzmeier, Nicolai, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, et al. “Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.Mol Neurodegener 15, no. 1 (October 8, 2020): 57. https://doi.org/10.1186/s13024-020-00407-2.
Franzmeier N, Suárez-Calvet M, Frontzkowski L, Moore A, Hohman TJ, Morenas-Rodriguez E, et al. Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration. Mol Neurodegener. 2020 Oct 8;15(1):57.
Franzmeier, Nicolai, et al. “Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration.Mol Neurodegener, vol. 15, no. 1, Oct. 2020, p. 57. Pubmed, doi:10.1186/s13024-020-00407-2.
Franzmeier N, Suárez-Calvet M, Frontzkowski L, Moore A, Hohman TJ, Morenas-Rodriguez E, Nuscher B, Shaw L, Trojanowski JQ, Dichgans M, Kleinberger G, Haass C, Ewers M, Alzheimer’s Disease Neuroimaging Initiative (ADNI). Higher CSF sTREM2 attenuates ApoE4-related risk for cognitive decline and neurodegeneration. Mol Neurodegener. 2020 Oct 8;15(1):57.
Journal cover image

Published In

Mol Neurodegener

DOI

EISSN

1750-1326

Publication Date

October 8, 2020

Volume

15

Issue

1

Start / End Page

57

Location

England

Related Subject Headings

  • Receptors, Immunologic
  • Neurology & Neurosurgery
  • Nerve Degeneration
  • Membrane Glycoproteins
  • Male
  • Humans
  • Genetic Predisposition to Disease
  • Female
  • Cognitive Dysfunction
  • Apolipoprotein E4