TREM2 Protein Expression Changes Correlate with Alzheimer's Disease Neurodegenerative Pathologies in Post-Mortem Temporal Cortices

Brain Pathol. 2015 Jul;25(4):469-80. doi: 10.1111/bpa.12190. Epub 2014 Nov 11.


Triggering receptor expressed by myeloid cells 2 (TREM2), a member of the immunoglobulin superfamily, has anti-inflammatory phagocytic function in myeloid cells. Several studies have shown that TREM2 gene variant rs75932628-T increased the risks for Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia and amyotrophic lateral sclerosis. It has been suggested that the risks could be resulted from the loss of TREM2 function caused by the mutation. Indeed, new evidence showed that several mutations in the immunoglobulin-like V-region led to low cell surface expression of TREM2 and reduced phagocytic function. Because of the emerging importance in understanding TREM2 expression and functions in human neurodegenerative diseases, we conducted biochemical and morphological studies of TREM2 expression in human post-mortem temporal cortical samples from AD and normal cases. Increased expression of TREM2 protein was found to significantly correlate with increases of phosphorylated-tau and active caspase 3, a marker of apoptosis, and also loss of the presynaptic protein SNAP25. Strong intensities of TREM2 immunoreactivity were observed in the microglia associated with amyloid plaques and in neuritic pathology-enriched areas. Based on the findings that TREM2 expression correlated with neurodegenerative markers, further investigation on whether there is abnormality of TREM2 functions in AD brains with nonmutated TREM2 is needed.

Keywords: TREM2; amyloid; brain; human; microglia; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Analysis of Variance
  • Caspase 3 / metabolism
  • Female
  • Gene Expression Regulation / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / metabolism
  • Microglia / metabolism
  • Microglia / pathology
  • Neurodegenerative Diseases / etiology*
  • Neurodegenerative Diseases / pathology*
  • Polymorphism, Single Nucleotide / genetics
  • Postmortem Changes
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Statistics, Nonparametric
  • Synaptosomal-Associated Protein 25 / metabolism
  • Temporal Lobe / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Glial Fibrillary Acidic Protein
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Immunologic
  • Synaptosomal-Associated Protein 25
  • TREM2 protein, human
  • TYROBP protein, human
  • Caspase 3