Cerebrospinal fluid soluble TREM2 in aging and Alzheimer's disease

• Published in: Alzheimer's research & therapy Vol. 8; no. 1; p. 17
• Main Authors: Henjum, Kristi, Almdahl, Ina S, Årskog, Vibeke, Minthon, Lennart, Hansson, Oskar, Fladby, Tormod, Nilsson, Lars N G
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.04.2016; BioMed Central
• Subjects: Aged; Aged, 80 and over; Aging; Aging - cerebrospinal fluid; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta; Amyloid beta-Peptides - cerebrospinal fluid; Analysis; Basic Medicine; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cognitive Dysfunction - cerebrospinal fluid; Diagnosis; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Membrane Glycoproteins - cerebrospinal fluid; Microgliosis; Middle Aged; Mild cognitive impairment; Neuroinflammation; Neurosciences; Neurovetenskaper; Peptide Fragments - cerebrospinal fluid; Receptors, Immunologic; Soluble TREM2; Tau; tau Proteins - cerebrospinal fluid; United States; Amyloid beta; Alzheimer’s disease; Mild cognitive impairment; Soluble TREM2; Aging; Microgliosis; Neuroinflammation; Tau
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-016-0182-1

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). 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). 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). 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.