Human macrophages stained with TREM2 (red) and MS4A4A (green) proteins. Little is known about MS4A4A function in the brain, but the protein may affect soluble TREM2 levels. Scale bar is 10 µm. 

Variants within a specific gene cluster can either raise or lower a person’s risk of developing Alzheimer’s disease, researchers reported August 14 in Science Translational Medicine. The authors analyzed the DNA of 813 older adults and sampled their cerebrospinal fluid for soluble TREM2, a protein that helps immune cells in the brain clear away excess amyloid and tau protein. They spotted two distinct patterns of mutation in the MS4A gene cluster, previously linked to Alzheimer’s. One variation was linked to low levels of soluble TREM2 and a high risk of developing the disease, the second to high TREM2 levels and a low risk. 

“We have provided strong evidence of a biological...

MS4A4A (green) and TREM2 (red) proteins were localized to the plasma membrane and organelles of human macrophages. Scale bar is 10 µm.

Y. Deming et al., “The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer’s disease risk,” doi:10.1126/scitranslmed.aau2291, Sci Transl Med, 2019.

Nicoletta Lanese is an intern at The Scientist. Email her at

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