Neuroinflammatory Phenotypes and Their Roles in Alzheimer's Disease

Background: Alzheimer's disease (AD) is characterized pathologically by the presence of amyloid plaques and neurofibrillary tangles in the brain. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. Objective: The goal of the study is to assess the neuroinflarnmatory state of the early and late AD brain using the macrophage categorizations of M1, M2a, M2b and M2c. Methods: We used quantitative real-time RT-PCR to assess a number of inflammatory markers in the frontal cortex and cerebellar tissue from early and late AD patients. We then used neuropathological and clinical outcomes to determine whether there were any correlations. Results: We found that the AD brain is capable of generating all macrophage-like responses. In addition, we found that early AD is distinct from late AD with respect to the inflammatory profiles expressed in the brain. Most interestingly, however, we found that the early AD samples were biased to one of two phenotypes, M1 or M2a. Conclusion: Heterogeneity in the neuroinflammatory state of the early AD brain may represent a source of variability among the AD population. It may also reflect the presence of comorbidities. (C) 2013 S. Karger AG, Basel