A valid quantitative imaging method for the measurement of amyloid deposition in humans could improve Alzheimer's disease (AD) diagnosis and antiamyloid therapy assessment. Our group developed Pittsburgh Compound-B (PIB), an amyloid-binding radiotracer, for positron emission tomography (PET). The current study was aimed to further validate PIB PET through quantitative imaging (arterial input) and inclusion of subjects with mild cognitive impairment (MCI). Pittsburgh Compound-B studies were performed in five AD, five MCI, and five control subjects and five subjects were retested within 20 days. Magnetic resonance images were acquired for partial volume correction and region-of-interest definition (e.g., posterior cingulate: PCG; cerebellum: CER). Data were analyzed using compartmental and graphical approaches. Regional distribution volume (DV) values were normalized to the reference region (CER) to yield DV ratios (DVRs). Good agreement was observed between compartmental and Logan DVR values (e.g., PCG: r=0.89, slope=0.91); the Logan results were less variable. Nonspecific PIB retention was similar across subjects (n=15, Logan CER DV: 3.63+/-0.48). Greater retention was observed in AD cortical areas, relative to controls (P<0.05). The PIB retention in MCI subjects appeared either 'AD-like' or 'control-like'. The mean test/retest variation was approximately 6% in primary areas-of-interest. The Logan analysis was the method-of-choice for the PIB PET data as it proved stable, valid, and promising for future larger studies and voxel-based statistical analyses. This study also showed that it is feasible to perform quantitative PIB PET imaging studies that are needed to validate simpler methods for routine use across the AD disease spectrum.

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The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-␤ protein is an initiating event in Alzheimer's disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (n ϭ 5) and symptomatic (n ϭ 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (n ϭ 2) were studied with PiB-PET imaging and compared with sporadic AD subjects (n ϭ 12) and controls from the general population (n ϭ 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35-49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms.

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