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

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 BP_ND) 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.

Keywords: Alzheimer's disease; Amyloid PET; Microglial activation; Positron emission tomography; Tau PET.