TREM 2 Protein Expression Changes Correlate with A lzheimer's Disease Neurodegenerative Pathologies in Post‐Mortem Temporal Cortices

• Published in: Brain pathology (Zurich, Switzerland) Vol. 25; no. 4; pp. 469 - 480
• Main Authors: Lue, Lih‐Fen, Schmitz, Christopher T., Serrano, Geidy, Sue, Lucia I., Beach, Thomas G., Walker, Douglas G.
• Format: Journal Article
• Language: English
• Published: 01.07.2015
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12190

Abstract Triggering receptor expressed by myeloid cells 2 ( TREM 2), a member of the immunoglobulin superfamily, has anti‐inflammatory phagocytic function in myeloid cells. Several studies have shown that TREM 2 gene variant rs75932628‐ T increased the risks for A lzheimer's disease ( AD ), P arkinson's disease, frontotemporal dementia and amyotrophic lateral sclerosis. It has been suggested that the risks could be resulted from the loss of TREM 2 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 TREM 2 and reduced phagocytic function. Because of the emerging importance in understanding TREM 2 expression and functions in human neurodegenerative diseases, we conducted biochemical and morphological studies of TREM 2 expression in human post‐mortem temporal cortical samples from AD and normal cases. Increased expression of TREM 2 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 SNAP 25. Strong intensities of TREM 2 immunoreactivity were observed in the microglia associated with amyloid plaques and in neuritic pathology‐enriched areas. Based on the findings that TREM 2 expression correlated with neurodegenerative markers, further investigation on whether there is abnormality of TREM 2 functions in AD brains with nonmutated TREM 2 is needed.