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These amyloid lesions provoke microglial activation, and recent neuroimaging technologies have enabled visualization of this response in living brains using radioligands for the peripheral benzodiazepine receptor also known as the 18 kDa translocator protein (TSPO). Here, we elucidated contributions of A\u03b2 and tau deposits to<jats:italic>in vivo<\/jats:italic>TSPO signals in pursuit of mechanistic and diagnostic significance of TSPO imaging in AD and other tauopathies. A new antibody to human TSPO revealed induction of TSPO-positive microgliosis by tau fibrils in tauopathy brains. Emergence of TSPO signals before occurrence of brain atrophy and thioflavin-S-positive tau amyloidosis was also demonstrated in living mice transgenic for mutant tau by positron emission tomography (PET) with two classes of TSPO radioligands, [<jats:sup>11<\/jats:sup>C]AC-5216 and [<jats:sup>18<\/jats:sup>F]fluoroethoxy-DAA1106. Meanwhile, only modest TSPO elevation was observed in aged mice modeling A\u03b2 plaque deposition, despite the notably enhanced<jats:italic>in vivo<\/jats:italic>binding of amyloid radiotracer, [<jats:sup>11<\/jats:sup>C]Pittsburgh Compound-B, to plaques. In these animals, [<jats:sup>11<\/jats:sup>C]AC-5216 yielded better TSPO contrasts than [<jats:sup>18<\/jats:sup>F]fluoroethoxy-DAA1106, supporting the possibility of capturing early neurotoxicity with high-performance TSPO probes. Furthermore, an additional line of mice modeling intraneuronal A\u03b2 accumulation displayed elevated TSPO signals following noticeable neuronal loss, unlike TSPO upregulation heralding massive neuronal death in tauopathy model mice. Our data corroborate the utility of TSPO-PET imaging as a biomarker for tau-triggered toxicity, and as a complement to amyloid scans for diagnostic assessment of tauopathies with and without A\u03b2 pathologies.<\/jats:p>","DOI":"10.1523\/jneurosci.3076-10.2011","type":"journal-article","created":{"date-parts":[[2011,3,23]],"date-time":"2011-03-23T16:53:58Z","timestamp":1300899238000},"page":"4720-4730","source":"Crossref","is-referenced-by-count":121,"title":["<i>In Vivo<\/i>Positron Emission Tomographic Imaging of Glial Responses to Amyloid-\u03b2 and Tau Pathologies in Mouse Models of Alzheimer's Disease and Related 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