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

• Published in: Neurobiology of disease Vol. 117; pp. 211 - 216
• Main Authors: Parbo, Peter, Ismail, Rola, Sommerauer, Michael, Stokholm, Morten G., Hansen, Allan K., Hansen, Kim V., Amidi, Ali, Schaldemose, Jeppe L., Gottrup, Hanne, Brændgaard, Hans, Eskildsen, Simon F., Borghammer, Per, Hinz, Rainer, Aanerud, Joel, Brooks, David J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2018; Elsevier
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid PET; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - metabolism; Cross-Sectional Studies; Early Diagnosis; Female; Humans; Inflammation - diagnostic imaging; Inflammation - metabolism; Male; Microglial activation; Middle Aged; Positron emission tomography; Positron-Emission Tomography - methods; Protein Aggregation, Pathological - diagnostic imaging; Protein Aggregation, Pathological - metabolism; Tau PET; tau Proteins - metabolism; PK11195; PiB; ROI; Aβ; flortaucipir; SPM; Amyloid PET; Tau PET; MMSE; SUVR; BPND; Alzheimer's disease; Positron emission tomography; Microglial activation; BPM
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2018.06.004

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. •Microglial activation is an early event in Alzheimer's disease neuropathology.•Inflammation can be seen in prodromal AD in the absence of detectable tau deposition.•Early inflammation may initially be a protective mechanism that subsequently fails.