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The effects of normal aging on amyloid-? deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

ABSTRACT: In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology.PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-? deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matter as the reference region.Multiple linear regression revealed slight but highly significant (corrected P < .05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex.There is an age-related amyloid-? deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.

SUBMITTER: Lao PJ

PROVIDER: S-EPMC4677061 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

Lao Patrick J PJ Betthauser Tobey J TJ Hillmer Ansel T AT Price Julie C JC Klunk William E WE Mihaila Iulia I Higgins Andrew T AT Bulova Peter D PD Hartley Sigan L SL Hardison Regina R Tumuluru Rameshwari V RV Murali Dhanabalan D Mathis Chester A CA Cohen Annie D AD Barnhart Todd E TE Devenny Darlynne A DA Mailick Marsha R MR Johnson Sterling C SC Handen Benjamin L BL Christian Bradley T BT

Alzheimer's & dementia : the journal of the Alzheimer's Association 20150613 4

<h4>Introduction</h4>In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology.<h4>Methods</h4>PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matt ...[more]

PMID: 26079411

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Project description:ObjectivesTo image amyloid deposition in patients with traumatic brain injury (TBI) using carbon 11-labeled Pittsburgh Compound B ([11C]PiB) positron emission tomography (PET) and to validate these findings using tritium-labeled PiB ([3H]PiB) autoradiography and immunocytochemistry in autopsy-acquired tissue.Design, setting, and participantsIn vivo PET at tertiary neuroscience referral center and ex vivo immunocytochemistry of autopsy-acquired brain tissue from a neuropathology archive. [11C]PiB PET was used to image amyloid deposition in 11 controls (median [range] age, 35 [24-60] years) and in 15 patients (median [range] age, 33 [21-50] years) between 1 and 361 days after a TBI. [3H]PiB autoradiography and immunocytochemistry for β-amyloid (Aβ) and β-amyloid precursor protein in brain tissue were obtained from separate cohorts of 16 patients (median [range] age, 46 [21-70] years) who died between 3 hours and 56 days after a TBI and 7 controls (median [range] age, 61 [29-71] years) who died of other causes.Main outcomes and measuresWe quantified the [11C]PiB distribution volume ratio and standardized uptake value ratio in PET images. The distribution volume ratio and the standardized uptake value ratio were measured in cortical gray matter, white matter, and multiple cortical and white matter regions of interest, as well as in striatal and thalamic regions of interest. We examined [3H]PiB binding and Aβ and β-amyloid precursor protein immunocytochemistry in autopsy-acquired brain tissue.ResultsCompared with the controls, the patients with TBI showed significantly increased [11C]PiB distribution volume ratios in cortical gray matter and the striatum (corrected P < .05 for both), but not in the thalamus or white matter. Increases in [11C]PiB distribution volume ratios in patients with TBI were seen across most cortical subregions, were replicated using comparisons of standardized uptake value ratios, and could not be accounted for by methodological confounders. Autoradiography revealed [3H]PiB binding in neocortical gray matter, in regions where amyloid deposition was demonstrated by immunocytochemistry; white matter showed Aβ and β-amyloid precursor protein by immunocytochemistry, but no [3H]PiB binding. No plaque-associated amyloid immunoreactivity or [3H]PiB binding was seen in cerebellar gray matter in autopsy-acquired tissue from either controls or patients with TBI, although 1 sample of cerebellar tissue from a patient with TBI showed amyloid angiopathy in meningeal vessels.Conclusions and relevance[11C]PiB shows increased binding following TBI. The specificity of this binding is supported by neocortical [3H]PiB binding in regions of amyloid deposition in the postmortem tissue of patients with TBI. [11C]PiB PET could be valuable in imaging amyloid deposition following TBI.

Project description:BackgroundUnderstanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [18F]Flutemetamol (FMT) and [11C]PiB (PiB) PET in the same people.MethodsStructural MRI, FMT PET and PiB PET were each performed in 30 young cognitively normal (yCN), 31 elderly cognitively normal (eCN) and 21 Alzheimer's disease dementia (AD) participants. PiB and FMT images for each participant were compared quantitatively using voxel- and region-based analyses. Region of interest (ROI) analyses included comparisons of grey matter (GM) regions as well as white matter (WM) regions. Regional comparisons of each tracer between different groups and comparisons of the two modalities within the different groups were performed. To compare mean SUVr between modalities, and between diagnostic groups, we used paired t-tests and Student's t-test, respectively. We also compared the ability of the two tracers to discriminate between diagnostic groups using AUROC estimates. The effect of using different normalization regions on SUVr values was also evaluated.ResultsBoth FMT and PiB showed greater uptake throughout GM structures in AD vs. eCN or yCN. In all dual-modality group comparisons (FMT vs. PiB in yCN, eCN, and AD), greater WM uptake was seen with FMT vs. PiB. In yCN and eCN greater diffuse GM uptake was seen with FMT vs. PiB. When comparing yCN to eCN within each tracer, greater WM uptake was seen in eCN vs yCN.ConclusionsFlutemetamol and PiB show similar topographical GM uptake in AD and CN participants and the tracers show comparable group discrimination. Greater WM accumulation with FMT suggests that quantitative differences vs. PiB will be apparent when using WM or GM as a reference region. Both imaging tracers demonstrate increased WM uptake in older people. These findings suggest that using different amyloid tracers or different methods of analyses in serial brain imaging in an individual may result in artifactual amyloid change measurements. Clinical use of several amyloid tracers in the same patient will have challenges that need to be carefully considered.

Dataset Information

The effects of normal aging on amyloid-? deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

Publications

The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

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