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. 2019 Nov 25:11:654-658.
doi: 10.1016/j.dadm.2019.04.006. eCollection 2019 Dec.

Longitudinal trajectories of amyloid deposition, cortical thickness, and tau in Down syndrome: A deep-phenotyping case report

Elijah Mak  1 , Anastasia Bickerton  1 , Concepcion Padilla  1 , Madeleine J Walpert  1 , Tiina Annus  1 , Liam R Wilson  1 , Young T Hong  2 , Tim D Fryer  2 , Jonathan P Coles  3 , Franklin I Aigbirhio  2 , Bradley T Christian  4 , Benjamin L Handen  5 , William E Klunk  5 , David K Menon  3 , Peter J Nestor  6 , Shahid H Zaman  1 , Anthony J Holland  1
Affiliations
Free PMC article

Longitudinal trajectories of amyloid deposition, cortical thickness, and tau in Down syndrome: A deep-phenotyping case report

Elijah Mak et al. Alzheimers Dement (Amst). .
Free PMC article

Abstract

Introduction: Comorbid Alzheimer disease pathologies are frequently found in people with Down syndrome (DS). We report a deep phenotyping study undertaken over 7 years in a participant with DS who was nondemented at baseline but developed dementia after 5 years.

Methods: Throughout the course of the study, the participant was seen 4 times (2010, 2013, 2015, and 2017). Multimodal neuroimaging, including three serial scans of [11C]-PiB-PET, four structural magnetic resonance imagings, as well as a [18F]-AV1451 scan, was interpreted alongside detailed neuropsychological assessments over the study period.

Results: Amyloid beta accumulation preceded the onset of dementia and cognitive decline, which in turn corresponded to the predominant deposition of tau in temporoparietal cortices.

Discussion: Until now, data on the longitudinal trajectories of amyloid accumulation, tau pathology, and brain atrophy over multiple time points remain scarce in DS. This case report highlights the potential for deep phenotyping imaging to elucidate the substrates of cognitive decline in DS, although further longitudinal studies are necessary to clarify the relative contributions of both amyloid and tau.

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Figures

Fig. 1
Fig. 1
Trajectory of structural atrophy, Aβ accumulation over 3 timepoints and tau deposition at timepoint 4. Top row: Across the timepoints, structural MRI revealed progressive ventricular dilatation and subtle hippocampal atrophy with respect to baseline (blue voxels). Middle row: Peak regions of amyloid accumulation were distributed in posterior regions, such as the precuneus. Over the course of study, the spatial extent of amyloid increased to encompass temporal regions. Bottom row: At T4, [18F]-AV1451 scan showed a stereotypical pattern of AD tau distribution that involved the bilateral precuneus and temporoparietal cortices. Abbreviations: Aβ, amyloid β; AD, Alzheimer's disease; MRI, magnetic resonance imaging.
Fig. 2
Fig. 2
Contrasting longitudinal trajectories associated with Aβ accumulation and cortical thinning across the cortex. The sharp increase of Aβ at T2 relative to T1 was followed by a plateau at T3, whereas cortical thickness continued to decrease across all timepoints. Abbreviation: Aβ, amyloid β.
Fig. 3
Fig. 3
Regional distribution of Aβ accumulation from baseline to 59 months. A: Heatmap of [11C]-PiB BPND across the cortex. B: Annualized rate of Aβ accumulation in cortical regions. Abbreviation: Aβ, amyloid β.
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