Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study

• DOI: 10.1016/j.nbd.2018.06.004
• Publication Date: 2018-06-11T11:50:21Z
• Authors: Peter Parbo; Rola Ismail; Michael Sommerauer; Morten G. Stokholm; Allan K. Hansen; Kim V. Hansen; Ali Amidi; Jeppe L. Schaldemose; Hanne Gottrup; Hans Brændgaard; Simon F. Eskildsen; Per Borghammer; Rainer Hinz; Joel Aanerud; David J. Brooks
• Keywords: Amyloid (mycology); Statistical parametric mapping; Temporal cortex

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).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.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.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.