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Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease

Henjum, Kristi; Almdahl, Ina S.; Årskog, Vibeke; Minthon, Lennart LU ; Hansson, Oskar LU ; Fladby, Tormod and Nilsson, Lars N G (2016) In Alzheimer's Research & Therapy 8(1).
Abstract

Background: Alzheimer's disease (AD) neuropathology is associated with neuroinflammation, but there are few useful biomarkers. Mutant variants of triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to late-onset AD and other neurodegenerative disorders. TREM2, a microglial receptor, is involved in innate immunity. A cleaved fragment, soluble TREM2 (sTREM2), is present in the cerebrospinal fluid (CSF). Methods: We developed and used a novel enzyme-linked immunosorbent assay to investigate the potential value of CSF sTREM2 as an AD biomarker in two independent cohorts: an AD/mild cognitive impairment (MCI)/control cohort (n = 100) and an AD/control cohort (n = 50). Results: We found no significant difference... (More)

Background: Alzheimer's disease (AD) neuropathology is associated with neuroinflammation, but there are few useful biomarkers. Mutant variants of triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to late-onset AD and other neurodegenerative disorders. TREM2, a microglial receptor, is involved in innate immunity. A cleaved fragment, soluble TREM2 (sTREM2), is present in the cerebrospinal fluid (CSF). Methods: We developed and used a novel enzyme-linked immunosorbent assay to investigate the potential value of CSF sTREM2 as an AD biomarker in two independent cohorts: an AD/mild cognitive impairment (MCI)/control cohort (n = 100) and an AD/control cohort (n = 50). Results: We found no significant difference in sTREM2 levels between groups of controls and patients with AD or MCI. However, among all controls there was a positive correlation between sTREM2 and age (Spearman rho = 0.50; p <0.001; n = 75). In the AD/MCI/control cohort, CSF sTREM2 correlated positively with total Tau (T-tau) (Spearman rho 0.57; p <0.001; n = 50), phosphorylated Tau (P-tau) (Spearman rho 0.63; p <0.001; n = 50) and amyloid-β1-42 (Aβ42) (Spearman rho 0.35; p = 0.01; n = 50) in control subjects. Among controls with a CSF Aβ42 above a cut-off value (700 pg/ml) in this cohort, the positive correlation between sTREM2 and Aβ42 was stronger (Spearman rho = 0.44; p = 0.002; n = 46). Conclusions: sTREM2 in CSF correlates with aging in controls, and with the neurodegenerative markers CSF T-tau/P-tau among controls who are negative for AD CSF core biomarkers Aβ42, T-tau or P-tau.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aging, Alzheimer's disease, Amyloid beta, Microgliosis, Mild cognitive impairment, Neuroinflammation, Soluble TREM2, Tau
in
Alzheimer's Research & Therapy
volume
8
issue
1
publisher
BioMed Central
external identifiers
  • Scopus:84964989681
  • WOS:000374816600001
ISSN
1758-9193
DOI
10.1186/s13195-016-0182-1
language
English
LU publication?
yes
id
bf6411c3-1b75-4d4e-a0b6-718e0787b3a4
date added to LUP
2016-06-01 15:27:44
date last changed
2017-01-08 05:54:54
@article{bf6411c3-1b75-4d4e-a0b6-718e0787b3a4,
  abstract     = {<p>Background: Alzheimer's disease (AD) neuropathology is associated with neuroinflammation, but there are few useful biomarkers. Mutant variants of triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to late-onset AD and other neurodegenerative disorders. TREM2, a microglial receptor, is involved in innate immunity. A cleaved fragment, soluble TREM2 (sTREM2), is present in the cerebrospinal fluid (CSF). Methods: We developed and used a novel enzyme-linked immunosorbent assay to investigate the potential value of CSF sTREM2 as an AD biomarker in two independent cohorts: an AD/mild cognitive impairment (MCI)/control cohort (n = 100) and an AD/control cohort (n = 50). Results: We found no significant difference in sTREM2 levels between groups of controls and patients with AD or MCI. However, among all controls there was a positive correlation between sTREM2 and age (Spearman rho = 0.50; p &lt;0.001; n = 75). In the AD/MCI/control cohort, CSF sTREM2 correlated positively with total Tau (T-tau) (Spearman rho 0.57; p &lt;0.001; n = 50), phosphorylated Tau (P-tau) (Spearman rho 0.63; p &lt;0.001; n = 50) and amyloid-β1-42 (Aβ42) (Spearman rho 0.35; p = 0.01; n = 50) in control subjects. Among controls with a CSF Aβ42 above a cut-off value (700 pg/ml) in this cohort, the positive correlation between sTREM2 and Aβ42 was stronger (Spearman rho = 0.44; p = 0.002; n = 46). Conclusions: sTREM2 in CSF correlates with aging in controls, and with the neurodegenerative markers CSF T-tau/P-tau among controls who are negative for AD CSF core biomarkers Aβ42, T-tau or P-tau.</p>},
  articleno    = {182},
  author       = {Henjum, Kristi and Almdahl, Ina S. and Årskog, Vibeke and Minthon, Lennart and Hansson, Oskar and Fladby, Tormod and Nilsson, Lars N G},
  issn         = {1758-9193},
  keyword      = {Aging,Alzheimer's disease,Amyloid beta,Microgliosis,Mild cognitive impairment,Neuroinflammation,Soluble TREM2,Tau},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Alzheimer's Research & Therapy},
  title        = {Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease},
  url          = {http://dx.doi.org/10.1186/s13195-016-0182-1},
  volume       = {8},
  year         = {2016},
}