Title: The striatum is an early, accurate indicator of amyloid burden using [11C]PiB in Down syndrome: Comparison of two radiotracers
Legend: (A) Average PiB and florbetapir (FBP) PET SUVR images by amyloid status. Percent difference images show the greatest PET signal in the precuneus and striatum for both tracers, though PiB has a greater dynamic range and shows much higher relative signal than FBP. (B) Difference in estimated time-to-positivity between the cortex and striatum-specific regions of interest (ROIs). ROIs include the caudate, putamen, accumbens, and a composite MRI-based striatum, all generated using the Harvard Oxford Atlas. Additionally, a PET-generated striatum ROI was created by thresholding the PiB difference image in Figure A to +0.75 SUVR. Differences in estimated time-to-positivity relative to the cortex were assessed with a one-tailed paired t-test, determining if each region shows earlier estimates than the cortex. PiB (B1) shows significantly earlier amyloid positivity in all regions except the caudate. FBP (B2) does not show any significant difference with the cortex. (C) Sampled iterative local approximation (SILA) models for the cortex and PET-based striatum ROIs of PiB (C1). To plot the cortex model along the striatum positivity axis, the cortex model was shifted by the average difference found in Figure B1 (3.40 years). Ratio of the striatum SILA model to the cortex SILA model is displayed in C2. All cortically Aβ-converting participants demonstrate earlier striatal positivity.
Citation: McLachlan, M., Bettcher, B., McVea, A., DiFilippo, A., Zammit, M., LeMerise, L., Rouanet, J., Price, J., Tudorascu, D., Laymon, C., Keator, D., Lao, P., Brickman, A. M., Fryer, T., Hartley, S., Ances, B. M., Rosas, H. D., Johnson, S., Betthauser, T., Stone, C. K., … Investigators, A. D. (2025). The striatum is an early, accurate indicator of amyloid burden using [11C]PiB in Down syndrome: Comparison of two radiotracers. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 21(4), e70141. https://doi.org/10.1002/alz.70141
Abstract:
Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [11C]Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging, which has not been replicated with [18F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.
Methods: Longitudinal PiB (n = 175 participants) and FBP (n = 92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome (ABC-DS) were used to measure cortical and striatal binding. Generalized temporal models for cortical and striatal amyloid accumulation were created using the sampled iterative local approximation (SILA) method.
Results: PiB demonstrated greater striatal-to-cortical ratios than FBP. SILA analysis revealed striatal amyloid burden occurs 3.40 (2.39) years earlier than the cortex in PiB. There was no difference between the cortex and striatum in FBP.
Discussion: Among adults with Down syndrome, the striatum consistently accumulates amyloid earlier than the cortex when measured with PiB. This suggests the striatum is more sensitive to the onset of PiB PET-detectable amyloid in Down syndrome.
Highlights: Striatal amyloid is detectable 3.4 years before the cortex using PiB PET in DS. Florbetapir PET does not detect early striatal amyloid accumulation in DS. White matter can be used as reference region in longitudinal florbetapir PET. SILA trajectory models can be used to compare regional estimates for age of onset.
Slide Author: Max McLachlan
Investigator: Bradley T Christian, PhD
About the Lab: Research in the Christian lab focuses on developing and translating novel PET methods for the study of neurodevelopment and neuropsychiatric illness. This involves using PET methodologies to investigate neurochemical changes in the brain and studying novel radioligands to characterize neurotransmitter-protein interactions and how they are influenced by development, genes, environment and drugs. These imaging methods are being applied to investigate the etiologies and mechanisms in diseases such as Down syndrome, affective disorders, schizophrenia, Alzheimer’s disease and Tourette syndrome.