A New Discovery of Alzheimer’s Disease—TREM2

  • Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the Center for Stroke and Dementia Research (ISD) at LMU Medical Center have found that a protein called TREM2 may have a mitigating effect on the course of Alzheimer's disease. In a new study led by Professor Christian Haass (LMU, DZNE) and Professor Michael Ewers (ISD, LMU), it was found that patients with higher levels of TREM2 in the cerebrospinal fluid (CSF) had a better prognosis than those with lower levels at different stages of Alzheimer's disease, an observation that provides a starting point for the development of new treatment strategies for Alzheimer's disease.


    In the brain, TREM2 is produced by microglia, which act as immune cells of the brain, and these cells patrol the brain, handling cellular waste and abnormal extracellular deposits. Earlier studies in mice by Haass and colleagues showed that TREM2 activation of microglia can encapsulate and selectively destroy toxic protein aggregates typical of Alzheimer's disease. These observations suggest that TREM2 may protect the brain from the degenerative effects of Alzheimer's disease. Whether this study is applicable to Alzheimer's disease patients based on mouse models remains unknown. In this regard, Ewers, Haass and their colleagues set out to establish a statistical correlation. Data collected from 385 patients in the Alzheimer's Disease Neuroimaging Initiative (ADNI) mainly include the TREM2 concentration in the CSF samples of the patient population and the disease progression rate of these patients over several years. It is important to note that these data are derived not only from Alzheimer's patients but also from healthy older adults who have been regularly examined for many years. The results of the statistical analysis of the data provided meaningful associations between changes in specific biochemical parameters and Alzheimer's clinical scores.


    Ewers and Haass demonstrated that the higher the TREM2 concentration, the better the prognosis at all stages of the disease. In these subjects, memory instability was ameliorated and the rate of contraction of the hippocampus, an area of the brain important for learning and memory, was relatively slow. The Ewers researchers say their findings have clinical implications because these patients continue to have a reduced risk of dementia over an 11-year period; however, activating microglia is a double-edged sword. In addition to providing protection, it may also contribute to the inflammatory response. Nevertheless, TREM2 may play a key role in triggering a protective immune response in the brain of Alzheimer's patients.

    The concentration of TREM2 in CSF usually increases at the early onset of symptoms in the disease. According to Haass, TREM2 is produced in response to brain damage that has already occurred, and this protein stimulates microglia to protect the brain. However, this protective effect seems insufficient for the treatment of Alzheimer's disease. Based on this, Haass and colleagues are developing a new therapeutic strategy to develop a therapeutic antibody that can stimulate TREM2 function, thereby improving its protective effects.