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

Authors
 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 
Citation
 BRAIN, Vol.136(Pt 7) : 2228-2238, 2013 
Journal Title
 BRAIN 
ISSN
 0006-8950 
Issue Date
2013
MeSH
Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging* ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism* ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism ; Analysis of Variance ; Aniline Compounds/pharmacokinetics ; Brain/metabolism* ; Brain/pathology ; Brain Mapping ; Cognition Disorders/diagnostic imaging ; Cognition Disorders/genetics ; Cognition Disorders/metabolism ; Cognition Disorders/pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Positron-Emission Tomography ; Psychiatric Status Rating Scales ; Pyrimidines/pharmacokinetics ; Receptors, GABA/genetics ; Receptors, GABA/metabolism* ; Statistics as Topic ; Thiazoles/pharmacokinetics
Keywords
Alzheimer’s disease ; mild cognitive impairment ; neuroinflammation ; positron emission tomography
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 (11)C-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 (11)C-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, (11)C-Pittsburgh Compound B binding, or age of onset. Patients with Alzheimer's disease, but not those with mild cognitive impairment, had greater (11)C-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. (11)C-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. (11)C-PBR28 binding also inversely correlated with grey matter volume. Early-onset (<65 years) patients had greater (11)C-PBR28 binding than late-onset patients, and in parietal cortex and striatum (11)C-PBR28 binding correlated with lower age of onset. Partial volume corrected and uncorrected results were generally in agreement; however, the correlation between (11)C-PBR28 and (11)C-Pittsburgh Compound B binding was seen only after partial volume correction. The results suggest that neuroinflammation, indicated by increased (11)C-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. (11)C-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.
Full Text
http://brain.oxfordjournals.org/content/136/7/2228.long
DOI
10.1093/brain/awt145
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87303
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