RT Journal Article SR Electronic T1 Early and longitudinal microglial activation but not amyloid accumulation predict cognitive outcome in PS2APP mice JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.118.217703 DO 10.2967/jnumed.118.217703 A1 Carola Focke A1 Tanja Blume A1 Benedikt Zott A1 Yuan Shi A1 Maximilian Deussing A1 Finn Peters A1 Claudio Schmidt A1 Gernot Kleinberger A1 Simon Lindner A1 Franz-Josef Gildehaus A1 Leonie Beyer A1 Barbara von Ungern-Sternberg A1 Peter Bartenstein A1 Laurence Ozmen A1 Karlheinz Baumann A1 Mario M Dorostkar A1 Christian Haass A1 Helmuth Adelsberger A1 Jochen Herms A1 Axel Rominger A1 Matthias Brendel YR 2018 UL http://jnm.snmjournals.org/content/early/2018/10/11/jnumed.118.217703.abstract AB Neuroinflammation may have beneficial or detrimental net effects on the cognitive outcome of Alzheimer’s disease patients (AD). 18kDa translocator protein (TSPO) imaging by positron-emission-tomography (PET) enables longitudinal monitoring of microglial activation in vivo. We compiled serial PET measures of TSPO and amyloid with terminal cognitive assessment (water maze) in an AD transgenic mouse model (PS2APP) from eight to 13 months of age, followed by immunohistochemical analyses of microglia, amyloid and synaptic density. Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at eight months. The progression of TSPO activation to 13 months also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the timepoint. This first PET investigation with longitudinal TSPO- and amyloid-PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.