A new positron emission tomography (PET) tracer called BU99008 detects reactive astrogliosis, a hallmark of Alzheimer's disease (AD) that occurs very early on, researchers say. The tracer is an astrocytic PET ligand targeting imidazoline-2 binding sites (I2BS) on astrocytes. "It is known that astrocytes are key elements for regulating the communication and activities of neuronal cells in our brains," Drs. Agneta Nordberg and Amit Kumar of the Karolinska Institute told Reuters Health in a joint email. "In different brain diseases, astrocytes seem to be able to initiate early defense processes, and thereby changes its properties into what is called 'reactive astrogliosis.'" "In earlier studies," they note, "we observed that increased astrogliosis is present early or even can precede other well-known pathological hallmarks such as amyloid plaque and tau tangles in AD." "The compound BU99008 was recently developed and had shown some promise in previous studies in healthy volunteers," they said. "This motivated us to further explore the properties of the PET tracer and its potential to visualize reactive astrocytes in Alzheimer brains." As reported in Molecular Psychiatry, the team investigated BU99008's potential as a biomarker for early detection of AD by analyzing postmortem brain tissue from six individuals with AD and seven controls without AD who died of other causes. They found that BU99008 could visualize reactive astrogliosis in postmortem AD brains, with regional binding studies demonstrating significantly higher binding in AD brain regions compared to controls. Comparative autoradiography studies reinforced the findings. The authors state in the paper, "The data clearly show that BU99008 could detect...reactive astrocytes with good selectivity and specificity and hence be a potential attractive clinical astrocytic PET tracer for gaining further insight into the role of reactive astrogliosis in AD." Drs. Nordberg and Kumar said, "Our next step is to use this new PET tracer for studying and characterizing possible reactive astrogliosis in non-AD dementia disorders, including different forms of frontal temporal dementia and Parkinson´s disease. We also aim to perform PET studies with BU99008 in different stages of AD, from presymptomatic to symptomatic, in early prodromal/preclinical AD, as well as in carriers of genetic AD mutations." Dr. Philip Stieg, Chairman and Neurosurgeon-in-Chief at New York-Presbyterian/Weill Cornell Medical Center and founder of the Weill Cornell Brain and Spine Center in New York City, commented by email. "Astrogliosis reflects a reaction to AD and is NOT involved in the cause of the disease. The tracer is useful for early detection but only in regard to the astroglial response; it does not provide information on other glial cells - i.e., microglia or oligodendrocytes." "We will need additional insight into the time frame of astrogliosis, and specific locations and relationships to the overall AD process," he said. "The astrogliosis response will need further analysis - linear, cyclical, early and late or variable during the disease." Another question, he noted, is whether the early response seen in the study plays a role in protection or disease progression. "This is possibly a good marker for early detection of AD and could be used in patients at high risk (i.e., homozygous for the APO4E gene). If astrogliosis is useful in containing the disease, it will be investigated from that perspective," Dr. Stieg concluded. —Marilynn Larkin Source
