Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease.
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.
Department of Pharmacology, University of Oslo and Oslo University Hospital, P.b. 1057, Blindern NO-0316, Oslo, Norway.
Kristi
K
Henjum
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.|Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
Ina S
IS
Almdahl
Department of Pharmacology, University of Oslo and Oslo University Hospital, P.b. 1057, Blindern NO-0316, Oslo, Norway.
Vibeke
V
Årskog
Department of Clinical Sciences Malmö, Memory Clinic, Clinical Memory Research Unit, Lund University, Malmö, Sweden.
Lennart
L
Minthon
Department of Clinical Sciences Malmö, Memory Clinic, Clinical Memory Research Unit, Lund University, Malmö, Sweden.
Oskar
O
Hansson
Department of Neurology, Akershus University Hospital, Lørenskog, Norway.|Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway.
Tormod
T
Fladby
Department of Pharmacology, University of Oslo and Oslo University Hospital, P.b. 1057, Blindern NO-0316, Oslo, Norway. lars.nilsson@medisin.uio.no.
Lars N G
LN
Nilsson
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011971:Receptors, Immunologic; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Aging; Alzheimer’s disease; Amyloid beta; Microgliosis; Mild cognitive impairment; Neuroinflammation; Soluble TREM2; Tau