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Mol Psychiatry. 2015 Dec;20(12):1579-87. doi: 10.1038/mp.2015.1. Epub 2015 Feb 24.

In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.

Suridjan I1,2, Pollock BG2,3,4, Verhoeff NP2,4,5, Voineskos AN1,2,3,4, Chow T1,2,4,5,6, Rusjan PM1, Lobaugh NJ1,6, Houle S1,4, Mulsant BH3,4, Mizrahi R1,2,4.

Author information

1
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
2
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
3
Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
4
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
5
Centre for Mental Health, Baycrest Health Sciences, Toronto, ON, Canada.
6
Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada.

Abstract

Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.

PMID:
25707397
DOI:
10.1038/mp.2015.1
[Indexed for MEDLINE]

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