Overview
To investigate the mechanisms underlying increased white matter hyperintensities and how elevated amyloid deposition affects adjacent white matter in Down syndrome (DS), we will retrospectively assess associations between antemortem amyloid positron emission tomography (PET), postmortem magnetic resonance imaging (MRI), and histopathology; prospectively acquire postmortem MRI to compare structural and diffusion MRI metrics. Identifying neuroimaging biomarkers may elucidate early events in Alzheimer’s progression and enhance the precision of screening adults with DS for clinical trials.
Our team in Pittsburgh serves as the central site for postmortem imaging of Down syndrome autopsy cases nationwide through the Alzheimer Biomarker Consortium – Down Syndrome (ABC-DS). We will leverage high-resolution MRI with advanced segmentation and registration methods to co-register with antemortem neuroimages and postmortem histology in the same subjects. Quantitative assessments of postmortem white matter abnormalities near amyloid-positive regions will highlight cerebrovascular pathologies in Down syndrome compared to a late-onset Alzheimer’s disease cohort from our Alzheimer's Disease Research Center (ADRC).
We aim to identify several neuroimaging features—both spatial patterns and protein biomarkers—to inform future research involving larger cohorts and investigate the utility of these biomarkers in the short term. Ultimately, this work may shed light on early events in Alzheimer's disease progression and enable more effective interventions tailored to the needs of people with Down syndrome.
Human Post-Mortem Imaging Sequences
| Purpose | Modality, Resolution |
|---|---|
| Brain morphometrics | T1w MP2RAGE, 0.37 mm iso |
| White matter hyperintensities | T2w SPACE, 0.4 mm iso |
| Cerebral microbleeds | T2* GRE, 0.37 mm iso |
| White matter microstructrual changes | DW-SSFP, 1.5 mm iso |
Autopsy Cases Imaged (2025-07-21)
| Pitt ADRC | 143 |
| ABC-DS | 32 |
| Total | 175 |
Recent Publications
- Liou JJ, Li J, Berardinelli J, Jin H, Santini T, Noh J, Farhat N, Wu M, Aizenstein HJ, Mettenburg JM, Yong WH, Head E, Ikonomovic MD, Ibrahim TS, Kofler JK; Alzheimer Biomarker Consortium—Down Syndrome. Correlating hippocampal and amygdala volumes with neuropathological burden in Down syndrome and Alzheimer's disease and related neurodegenerative pathologies using 7T postmortem MRI. J Neuropathol Exp Neurol. 2025 May 1;84(5):364-378. doi: 10.1093/jnen/nlaf010. PMID: 40063697; PMCID: PMC12012357.
- Liou JJ, Lou J, Flores-Aguilar L, Nakagiri J, Yong W, Hom CL, Doran EW, Totoiu MO, Lott I, Mapstone M, Keator DB, Brickman AM, Wright ST, Nelson B, Lai F, Xicota L, Dang LT, Li J, Santini T, Mettenburg JM, Ikonomovic MD, Kofler J, Ibrahim T, Head E; Alzheimer Biomarker Consortium ‐ Down Syndrome. A neuropathology case report of a woman with Down syndrome who remained cognitively stable: Implications for resilience to neuropathology. Alzheimers Dement. 2025 Feb;21(2):e14479. doi: 10.1002/alz.14479. Epub 2025 Jan 27. PMID: 39868632; PMCID: PMC11851131.
Funding
- Alzheimer Biomarker Consortium - Down Syndrome: U19 AG068054
- Pittsburgh Alzheimer's Disease Research Center: P30 AG066468
- BrightFocus Foundation: A2025009F
- Amyloid-Related Imaging Abnormalities: U24 NS141780
