In the brains of Alzheimer's diseases, there exist two abnormal structures -- amyloid plaques and neurofibrillary tangles— that consist of misfolded proteins. Amyloid plaques are made of a toxic protein called beta amyloid. Amyloid plaques are found in the spaces between the brain's nerve cells, and affect normal neuronal function and may eventually cause cell death. A protein called TREM2 that is located on immune cells in the brain has been found to act as a signaling receptor involved in innate immunity for the natural clearance of the toxic protein beta amyloid. TREM2 recruits immune cells in response to amyloid plaques but this process may also have harmful effects in the brain. TREM2 is a protein that is made in myeloid cells of the bone marrow. The TREM2 protein is located on the cell surface and can interact with the TYROBP proteins. This interaction helps transmit chemical signals to activate the cell. The TYROBP-TREM2 complex plays a role in the growth and development of immune cells. This complex activates these cells, triggering an inflammatory response to injury or disease. Recent studies have shown that patients with Alzheimer's tend to have more TREM2 variants. In addition, neuroinflammation is a key contributor to Alzheimer's. If we can identify the exact function of TREM2, it would help us understand how neuroinflammation contributes to Alzheimer's. Now, a new study appearing in the Journal of Neuroscience demonstrates that TREM2 plays distinct functional roles at different stages in Alzheimer's pathology. Using a mouse model of Alzheimer's disease, the researchers identified the effects of TREM2 deficiency. The study was carried out by Taylor Jay, Anna Hirsch, Margaret Broihier, Lee Neilson, and Gary Landreth from Western Reserve University, Crystal Miller from The Cleveland Clinic Lerner Research Institute, and Richard Ransohoff from Biogen. In the past, some scientists reported that Alzheimer's mice lacking TREM2 had more amyloid plaques. However, others came to the opposite conclusion: deleting TREM2 improved amyloid pathology. In the current study, the team sought to determine exactly how TREM2 influences amyloid pathology. They found that removing TREM2 ameliorated amyloid pathology in the early stage of the disease, but exacerbated it in the late stage. This explained why previous research had produce conflicting conclusions. The team will continue exploring the role of TREM2 and its partners in Alzheimer's pathogenesis in future research. (In addition, Cusabio provides a large number of proteins and antibodies such as TREM2 and Recombinant TLR2.)
