[11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease.
BACKGROUND
Beta-amyloid (Abeta) plaques are the hallmark of Alzheimer disease (AD). A PET imaging tracer that binds to Abeta plaques in vivo, N-methyl-[(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]PIB for "Pittsburgh Compound-B"), has significantly higher binding in subjects diagnosed with dementia of the Alzheimer type (DAT) compared to nondemented controls. The authors used this imaging technique to investigate whether abnormal binding occurs in clinically normal individuals, prior to the development of cognitive changes.


METHODS
Forty-one nondemented subjects (age range 20 to 86 years) and 10 patients with DAT (age range 66 to 86 years) underwent [(11)C]PIB PET scanning. Regions of interest were drawn on the MRI over the cerebellar, prefrontal, lateral temporal, occipital, gyrus rectus, precuneus, and striatal cortex. Binding potential values (BPs), proportional to the density of [(11)C]PIB-Abeta binding sites, were calculated using the Logan graphical analysis and the cerebellar cortex for a reference tissue.


RESULTS
Patients with DAT had elevated BP values vs nondemented subjects (p < 0.0001). Four of the 41 nondemented subjects had elevated cortical BP values and their BP values as a group were not significantly different from the DAT subjects' BP values. Two of these four nondemented subjects had [(11)C]PIB uptake, both visually and quantitatively, that was indistinguishable from the DAT subjects.


CONCLUSIONS
Elevated [(11)C]PIB binding in nondemented subjects suggests that [(11)C]PIB amyloid imaging may be sensitive for detection of a preclinical Alzheimer disease state. Longitudinal studies will be required to determine the association of elevated [(11)C]PIB binding and risk of developing dementia of the Alzheimer type.
Mintun
M A
MA
Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA. mintunm@mir.wustl.edu
Larossa
G N
GN
Sheline
Y I
YI
Dence
C S
CS
Lee
S Y
SY
Mach
R H
RH
Klunk
W E
WE
Mathis
C A
CA
DeKosky
S T
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Morris
J C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D002250:Carbon Radioisotopes; D006801:Humans; D008875:Middle Aged; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D015415:Biomarkers; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D013844:Thiazoles