Brad Christian, PhD – Slide of the Week

Title: Early striatal amyloid signal in Down Syndrome: Comparison of PiB and Florbetapir PET

Legend: PiB and florbetapir SUVR images at different stages of amyloid positivity, using an 18.1 CL threshold. MRI (left) highlights the striatum transaxially. Near the positivity threshold, PiB PET exhibits greater uptake in the striatum as compared to florbetapir.

Citation: MJ McLachlan, JC Price, CM Laymon, A Garimella, DB Keator, WC Kreisl, WE Klunk, TD Fryer, AK McVea, AH Difillipo, MD Zammit, and BT Christian (2022). Early striatal amyloid signal in Down Syndrome: Comparison of PiB and Florbetapir PET. AAIC 2022; San Diego, CA. Poster #62459.

Abstract: PET amyloid [11C]PiB imaging has revealed early detection of Aβ in the striatum in individuals with Down Syndrome (DS), a group carrying genetic risk for AD. The goal of this investigation is to examine striatal binding of [11C]PiB and [18F]florbetapir (FBP) to determine if similar striatal uptake profiles are observed in individuals with DS. PET scans were acquired as part of the ABC-DS study. DS participants were scanned with either PiB (n=204; ages 25-56 yrs) or FBP (n=84; ages 40-85 yrs) at seven academic sites. SUVR images were created with acquisition times of 50-70min for both radiotracers, using a whole cerebellar reference region. ROIs were defined for the anterior ventral striatum (AVS) and the full cortex which included the AVS (CTX). SUVR was then converted to centiloids (CL) using published methods (Klunk 2015) with DS-specific modifications, including AVS extraction and approximate CL_AVS. Aβ(+) was defined using a threshold of 18.1 CL in CTX ROI (Zammit 2021), categorizing Aβ(-) and Aβ(+) groups. Comparisons across PiB and FBP examined 1) the proportion of CL_AVS values exceeding the threshold in the Aβ(-) group and 2) the difference between CL_AVS and CL_CTX in the Aβ(+) group. 58/204 subjects (PiB) and 72/84 subjects (FBP) were Aβ(+). For the Aβ(-) comparison, elevated CL_AVS was detected in 16/146 (PiB) and 0/12 (FBP). For the Aβ(+) comparison, 52/58 (PiB) and 52/72 (FBP) had CL_AVS greater than their CL_CTX. PiB PET exhibited higher uptake in the striatum during early stages of amyloid deposition. PiB revealed a 3.3x greater difference than FBP between striatal to cortical SUVR in the Aβ(+) group. Neuropathological investigation is ongoing to characterize these differences in striatal binding in DS. Despite this difference in early-stage binding, both PiB and FBP demonstrate high sensitivity for determining the presence of Aβ in DS.

About the Lab: Our research 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.

Investigator: Brad Christian, PhD

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