HAI Book 2025 - Flipbook - Page 605
McLachlan, Max
141
The striatum is an early, accurate indicator of [C-11]PiB amyloid
burden for the Down syndrome population
Max McLachlan1, Julie Price2, Dana Tudorascu3, Charles Laymon3, Patrick Lao4, Ben Handen3,
Tim Fryer5, Beau Ances6, Sterling Johnson1, Tobey Betthauser1, Shahid Zaman5, Elizabeth
Head7, Mark Mapstone7, Brecca Bettcher1, Lisette LeMerise1, Andrew McVea1, Alexandra
DiFillipo1, Matthew Zammit1, Sigan Hartley1, Bradley Christian1
1
University of Wisconsin - Madison, Madison, WI, US
MGH Martinos Center, Harvard, Boston, MA, US
3
University of Pittsburgh, Pittsburgh, PA, US
4
Columbia University Irving Medical Center, New York, NY, US
5
University of Cambridge, Cambridge, GB
6
Washington University in St. Louis, St. Louis, MO, US
7
University of California, Irvine, Irvine, CA, US
2
Background: Early detection of amyloid burden will dictate the inclusion criteria of anti-amyloid clinical trials for
individuals with Down syndrome (DS). [11C]PiB PET imaging in the DS population has revealed the earliest
accumulation of ´ amyloid (A´) in the striatum, though its reliability has not been quantified. This work evaluates
the extent and magnitude of striatum-first amyloid accumulation in a DS cohort.
Methods: 175 participants with DS completed a total of 382 longitudinal PiB PET scans (Table 1). PET images were
realigned, summed 50-70min, smoothed to 8mm resolution, and spatially normalized to a DS-specific template
(Figure 1a). SUVR (whole cerebellum reference) was extracted for the GAINN cortical ROI and striatum-specific
ROIs (listed in Figure 1b). Positivity thresholds were calculated for each ROI with a 2-distribution Gaussian mixture
model (threshold=µlower+2*SDlower). Using the sampled iterative local approximation (SILA) method, the average rate
of change was calculated within discrete intervals, yielding generalized models for amyloid progression relative to
positivity in each ROI. The estimated time-to-amyloid-positivity was calculated by aligning participant trajectories
to the models. Paired t-tests evaluated the average differences in time-to-positivity.
Results: Figure 1b displays the difference in estimated time-to-positivity between the cortex and each striatumspecific ROI. The PET-based striatum shows the earliest sensitivity to amyloid, on average 3.31 (2.50)*** years
before the cortex. Figure 2 displays the cortical and striatal SILA models, as well as their ratio along the cortical
time-to-positivity axis. On average, the striatum is 16.5% (8.4%) higher than the cortex at time of cortical
positivity, and their ratio plateaus at 1.3.
Conclusion: The striatum is an early and accurate indicator of amyloid burden in the DS population. The PETbased striatum ROI shows the greatest sensitivity, while the caudate shows the highest variability, likely from
structural atrophy. Striatal amyloid binding is actively being characterized for [18F]florbetapir in DS.
HAI2025 - 605
