In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease

William C. Kreisl, Chul Hyoung Lyoo, Meghan McGwier, Joseph Snow, Kimberly J. Jenko, Nobuyo Kimura, Winston Corona, Cheryl L. Morse, Sami S. Zoghbi, Victor W. Pike, Francis J. McMahon, R. Scott Turner, Robert B. Innis

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255 Citations (Scopus)


Neuroinflammation is a pathological hallmark of Alzheimer's disease, but its role in cognitive impairment and its course of development during the disease are largely unknown. To address these unknowns, we used positron emission tomography with 11C-PBR28 to measure translocator protein 18 kDa (TSPO), a putative biomarker for inflammation. Patients with Alzheimer's disease, patients with mild cognitive impairment and older control subjects were also scanned with 11C-Pittsburgh Compound B to measure amyloid burden. Twenty-nine amyloid-positive patients (19 Alzheimer's, 10 mild cognitive impairment) and 13 amyloid-negative control subjects were studied. The primary goal of this study was to determine whether TSPO binding is elevated in patients with Alzheimer's disease, and the secondary goal was to determine whether TSPO binding correlates with neuropsychological measures, grey matter volume, 11C-Pittsburgh Compound B binding, or age of onset. Patients with Alzheimer's disease, but not those with mild cognitive impairment, had greater 11C-PBR28 binding in cortical brain regions than controls. The largest differences were seen in the parietal and temporal cortices, with no difference in subcortical regions or cerebellum. 11C-PBR28 binding inversely correlated with performance on Folstein Mini-Mental State Examination, Clinical Dementia Rating Scale Sum of Boxes, Logical Memory Immediate (Wechsler Memory Scale Third Edition), Trail Making part B and Block Design (Wechsler Adult Intelligence Scale Third Edition) tasks, with the largest correlations observed in the inferior parietal lobule. 11C-PBR28 binding also inversely correlated with grey matter volume. Early-onset (<65 years) patients had greater 11C-PBR28 binding than late-onset patients, and in parietal cortex and striatum 11C-PBR28 binding correlated with lower age of onset. Partial volume corrected and uncorrected results were generally in agreement; however, the correlation between 11C-PBR28 and 11C-Pittsburgh Compound B binding was seen only after partial volume correction. The results suggest that neuroinflammation, indicated by increased 11C-PBR28 binding to TSPO, occurs after conversion of mild cognitive impairment to Alzheimer's disease and worsens with disease progression. Greater inflammation may contribute to the precipitous disease course typically seen in early-onset patients. 11C-PBR28 may be useful in longitudinal studies to mark the conversion from mild cognitive impairment or to assess response to experimental treatments of Alzheimer's disease.

Original languageEnglish
Pages (from-to)2228-2238
Number of pages11
Issue number7
Publication statusPublished - 2013 Jul

Bibliographical note

Funding Information:
This project was funded in part by the Intramural Research Program of the National Institute of Mental Health-National Institutes of Health (IRP-NIMH-NIH), and as a public-private partnership supported by the NIMH and the Foundation for the NIH Biomarkers Consortium ( for the project ‘Measuring neuroinflammation in Alzheimer’s disease and mild cognitive impairment with 11C-PBR28 PET’. This project was submitted to the Biomarkers Consortium Neuroscience Steering Committee for execution and was managed by a Biomarkers Consortium Project Team that includes members from academia, Government, and the pharmaceutical industry. This work was supported by EMD Serono, Glaxo Smith Kline, Lilly, Merck, Pfizer, Inc., and Roche. We thank the Project Team for their contributions: Edilio Borroni (Roche), Linda Brady (NIMH), Thomas Finn (FDA), Richard Hargreaves (Merck), Robert Innis (NIMH), Walter Koroshetz (NINDS), William Kreisl (NIMH), Timothy McCarthy (Pfizer), P. David Mozley (Merck), Susanne Ostrowitzki (Roche), Victor Pike (NIMH), Eugenni Rabiner (GSK), Mark Shearman (EMD Serono), Judith Siuciak (FNIH), Cyrille Sur (Merck), Johannes Tauscher (Lilly).

Funding Information:
Additional support was provided by the American Academy of Neurology Foundation to William Kreisl. All authors have no conflicts of interest to disclose, financial or otherwise.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology


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