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

William C. Kreisl, Chulhyoung 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

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

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
JournalBrain
Volume136
Issue number7
DOIs
Publication statusPublished - 2013 Jan 1

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Alzheimer Disease
Parietal Lobe
Proteins
Amyloid
Age of Onset
Inflammation
(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
Wechsler Scales
Temporal Lobe
Intelligence
Short-Term Memory
Positron-Emission Tomography
Cerebellum
Longitudinal Studies
Dementia
Disease Progression
Cognitive Dysfunction
Biomarkers
Brain
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Kreisl, W. C., Lyoo, C., McGwier, M., Snow, J., Jenko, K. J., Kimura, N., ... Innis, R. B. (2013). In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. Brain, 136(7), 2228-2238. https://doi.org/10.1093/brain/awt145
Kreisl, William C. ; Lyoo, Chulhyoung ; McGwier, Meghan ; Snow, Joseph ; Jenko, Kimberly J. ; Kimura, Nobuyo ; Corona, Winston ; Morse, Cheryl L. ; Zoghbi, Sami S. ; Pike, Victor W. ; McMahon, Francis J. ; Turner, R. Scott ; Innis, Robert B. / In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. In: Brain. 2013 ; Vol. 136, No. 7. pp. 2228-2238.
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abstract = "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.",
author = "Kreisl, {William C.} and Chulhyoung Lyoo and Meghan McGwier and Joseph Snow and Jenko, {Kimberly J.} and Nobuyo Kimura and Winston Corona and Morse, {Cheryl L.} and Zoghbi, {Sami S.} and Pike, {Victor W.} and McMahon, {Francis J.} and Turner, {R. Scott} and Innis, {Robert B.}",
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Kreisl, WC, Lyoo, C, McGwier, M, Snow, J, Jenko, KJ, Kimura, N, Corona, W, Morse, CL, Zoghbi, SS, Pike, VW, McMahon, FJ, Turner, RS & Innis, RB 2013, 'In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease', Brain, vol. 136, no. 7, pp. 2228-2238. https://doi.org/10.1093/brain/awt145

In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease. / Kreisl, William C.; Lyoo, Chulhyoung; McGwier, Meghan; Snow, Joseph; Jenko, Kimberly J.; Kimura, Nobuyo; Corona, Winston; Morse, Cheryl L.; Zoghbi, Sami S.; Pike, Victor W.; McMahon, Francis J.; Turner, R. Scott; Innis, Robert B.

In: Brain, Vol. 136, No. 7, 01.01.2013, p. 2228-2238.

Research output: Contribution to journalArticle

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T1 - In vivo radioligand binding to translocator protein correlates with severity of Alzheimer's disease

AU - Kreisl, William C.

AU - Lyoo, Chulhyoung

AU - McGwier, Meghan

AU - Snow, Joseph

AU - Jenko, Kimberly J.

AU - Kimura, Nobuyo

AU - Corona, Winston

AU - Morse, Cheryl L.

AU - Zoghbi, Sami S.

AU - Pike, Victor W.

AU - McMahon, Francis J.

AU - Turner, R. Scott

AU - Innis, Robert B.

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N2 - 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.

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