title: In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.
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.
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Suridjan
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: B G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Centre for Mental Health, Baycrest Health Sciences, Toronto, ON, Canada.
authors.forename: N P L G
authors.initials: NP
authors.lastname: Verhoeff
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: A N
authors.initials: AN
authors.lastname: Voineskos
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Centre for Mental Health, Baycrest Health Sciences, Toronto, ON, Canada.|Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Chow
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: P M
authors.initials: PM
authors.lastname: Rusjan
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Medicine (Neurology), University of Toronto, Toronto, ON, Canada.
authors.forename: N J
authors.initials: NJ
authors.lastname: Lobaugh
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Houle
authors.affiliation: Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: B H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mizrahi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000813:Anilides; D003072:Cognition Disorders / Q000473:pathology; D004660:Encephalitis / Q000473:pathology*; D005260:Female; D005462:Fluorine Radioisotopes; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011725:Pyridines; D011869:Radioligand Assay; D066127:White Matter / Q000473:pathology*
chemical_list: D000813:Anilides; D005462:Fluorine Radioisotopes; C530438:N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride; D011725:Pyridines