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Brain inflammation accompanies amyloid in a majority of mild cognitive impairment cases due to Alzheimer’s disease

Lookup NU author(s): Professor Nicola PaveseORCiD, Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Subjects with amnestic mild cognitive impairment (MCI) associated with cortical beta-amyloid (Aβ) have a greatly increased risk of progressing to Alzheimer’s disease. We hypothesised that neuroinflammation occurs early in Alzheimer’s disease and would be present in most Aβ positive MCI cases. 11C-PiB (PiB) and 11C-(R)-PK11195 (PK11195) PET was used to determine the Aβ load and detect the extent of neuroinflammation (microglial activation) in 42 MCI cases. 12 agematched healthy controls (HC) had PiB PET and 10 HC had PK11195 PET for comparison. PiBpositivity was defined as target-to-cerebellar ratio above 1.5 within a composite cortical volume-ofinterest (VOI). Supervised cluster analysis was used to generate parametric maps of PK11195 binding potential (BP). Levels of PK11195 BP were measured in a composite cortical VOI and at a voxel level. Twenty-six of 42 (62%) MCI cases showed a raised cortical PiB RATIO compared to HC. Seventeen (65%) of these 26 PiB-positive MCI cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of PiB RATIO and PK11195 BP at a voxel level within subregions of frontal, parietal and temporal cortices. PK11195 PET reveals increased inflammation in a majority of Aβ positive MCI cases, its cortical distribution overlapping that of Aβ deposition.

Publication metadata

Author(s): Parbo P, Ismail R, Hansen K, Mårup F, Gottrup H, Braendgaard H, Eriksson B, Eskildsen S, Lund T, Tietze A, Edison P, Pavese N, Stokholm M, Borghammer P, Hinz R, Aanerud J, Brooks DJ

Publication type: Article

Publication status: Published

Journal: Brain

Year: 2017

Volume: 140

Issue: 7

Pages: 2002-2011

Print publication date: 01/07/2017

Online publication date: 28/05/2017

Acceptance date: 12/04/2017

Date deposited: 07/08/2017

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awx120


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