Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B

被引:3406
作者
Klunk, WE
Engler, H
Nordberg, A
Wang, YM
Blomqvist, G
Holt, DP
Bergström, M
Savitcheva, I
Huang, GF
Estrada, S
Ausén, B
Debnath, ML
Barletta, J
Price, JC
Sandell, J
Lopresti, BJ
Wall, A
Koivisto, P
Antoni, G
Mathis, CA
Långström, B
机构
[1] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA
[2] Uppsala Univ, PET Ctr, Uppsala Imanet AB, Uppsala, Sweden
[3] Huddinge Univ Hosp, Karolinska Inst, Neurotec Dept, Stockholm, Sweden
[4] Huddinge Univ Hosp, Dept Geriatr Med, Stockholm, Sweden
[5] Univ Pittsburgh, Dept Radiol, PET Facil, Pittsburgh, PA USA
[6] Uppsala Univ, Dept Organ Chem, Uppsala, Sweden
关键词
D O I
10.1002/ana.20009
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.
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页码:306 / 319
页数:14
相关论文
共 52 条
[1]   Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for β-amyloid plaques in Alzheimer's disease [J].
Agdeppa, ED ;
Kepe, V ;
Liu, J ;
Flores-Torres, S ;
Satyamurthy, N ;
Petric, A ;
Cole, GM ;
Small, GW ;
Huang, SC ;
Barrio, JR .
JOURNAL OF NEUROSCIENCE, 2001, 21 (24) :art. no.-RC189
[2]   Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer's disease treatment studies [J].
Alexander, GE ;
Chen, K ;
Pietrini, P ;
Rapoport, SI ;
Reiman, EM .
AMERICAN JOURNAL OF PSYCHIATRY, 2002, 159 (05) :738-745
[3]   Implementation and validation of a fully automatic system for intra- and interindividual registration of PET brain scans [J].
Andersson, JLR ;
Thurfjell, L .
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY, 1997, 21 (01) :136-144
[4]   The Topographical and Neuroanatomical Distribution of Neurofibrillary Tangles and Neuritic Plaques in the Cerebral Cortex of Patients with Alzheimer's Disease [J].
Arnold, Steven E. ;
Hyman, Bradley T. ;
Flory, Jill ;
Damasio, Antonio R. ;
Van Hoesen, Gary W. .
CEREBRAL CORTEX, 1991, 1 (01) :103-116
[5]   Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-β ligand in transgenic mice [J].
Bacskai, BJ ;
Hickey, GA ;
Skoch, J ;
Kajdasz, ST ;
Wang, YM ;
Huang, GF ;
Mathis, CA ;
Klunk, WE ;
Hyman, BT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (21) :12462-12467
[6]   Clinicopathologic studies in cognitively healthy aging and Alzheimer disease - Relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype [J].
Berg, L ;
McKeel, DW ;
Miller, JP ;
Storandt, M ;
Rubin, EH ;
Morris, JC ;
Baty, J ;
Coats, M ;
Norton, J ;
Goate, AM ;
Price, JL ;
Gearing, M ;
Mirra, SS ;
Saunders, AM .
ARCHIVES OF NEUROLOGY, 1998, 55 (03) :326-335
[7]   Positron emission tomography microdosing:: a new concept with application in tracer and early clinical drug development [J].
Bergström, M ;
Grahnén, A ;
Långström, B .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2003, 59 (5-6) :357-366
[8]   ALZHEIMERS-DISEASE - STRIATAL AMYLOID DEPOSITS AND NEUROFIBRILLARY CHANGES [J].
BRAAK, H ;
BRAAK, E .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1990, 49 (03) :215-224
[9]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[10]  
Brilliant MJ, 1997, NEUROPATH APPL NEURO, V23, P322, DOI 10.1046/j.1365-2990.1997.4198041.x