Peter Parbo1, Rola Ismail2, Michael Sommerauer3, Morten G Stokholm2, Allan K Hansen2, Kim V Hansen2, Ali Amidi4, Jeppe L Schaldemose2, Hanne Gottrup5, Hans Brændgaard5, Simon F Eskildsen6, Per Borghammer2, Rainer Hinz7, Joel Aanerud2, David J Brooks8. 1. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. Electronic address: peter.parbo@clin.au.dk. 2. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; Department of Neurology, University Hospital Cologne, Cologne, Germany. 4. Department of Psychology and Behavioural Sciences, Department of Oncology, Aarhus University & Aarhus University Hospital, Denmark. 5. Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 6. Center of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark. 7. Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK. 8. Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark; Division of Neuroscience, Newcastle University, Newcastle, UK.
Abstract
OBJECTIVE: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. RESULTS: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. INTERPRETATION: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.
OBJECTIVE: Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: Six clinically probable AD and 20 MCI subjects had inflammation (11C-(R)-PK11195), amyloid (11C-PiB) and tau (18F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses. RESULTS: 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11C-(R)-PK11195 BPND) and tau (18F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases. INTERPRETATION: While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.
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