Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer's disease

Alzheimers Dement. 2016 Dec;12(12):1259-1272. doi: 10.1016/j.jalz.2016.06.005. Epub 2016 Jul 14.


Introduction: TREM2 is involved in the regulation of inflammatory response and phagocytosis. A soluble fragment (sTREM2) is often found abnormally increased in cerebrospinal fluid (CSF) in Alzheimer's disease (AD).

Methods: One hundred fourteen participants (45 control, 19 preclinical, 27 mild cognitive impairment [MCI], and 23 AD) underwent CSF sTREM2 determination and magnetic resonance imaging (MRI). We studied the association between CSF sTREM2, gray matter volume, and water motion diffusivity and anisotropy across groups.

Results: In MCI patients, a positive correlation between CSF sTREM2 and gray matter volume was found in the bilateral inferior and middle temporal cortices, precuneus, the supramarginal, and angular gyri, after controlling by age, sex, and p-tau. A negative correlation with mean diffusivity was detected in overlapping regions, among others.

Discussion: In early AD, augmented CSF sTREM2 levels correspond with cerebral MRI features typical of brain swelling, supporting a role for TREM2 in the regulation of the neuroinflammatory response to early neurodegeneration.

Keywords: Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Neuroinflammation; TREM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / pathology
  • Female
  • Gray Matter / pathology*
  • Humans
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins