Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease
(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.
(Less)
- author
- Henjum, Kristi
; Almdahl, Ina S.
; Årskog, Vibeke
; Minthon, Lennart
LU
; Hansson, Oskar
LU
; Fladby, Tormod and Nilsson, Lars N G
- organization
- publishing date
- 2016
- 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
- article number
- 182
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:84964989681
- pmid:27121148
- 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
- 2025-01-11 07:05:37
@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 <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.</p>}}, 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}}, keywords = {{Aging; Alzheimer's disease; Amyloid beta; Microgliosis; Mild cognitive impairment; Neuroinflammation; Soluble TREM2; Tau}}, language = {{eng}}, number = {{1}}, publisher = {{BioMed Central (BMC)}}, 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}}, doi = {{10.1186/s13195-016-0182-1}}, volume = {{8}}, year = {{2016}}, }