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Summary
This summary is machine-generated.

Down syndrome (DS) individuals show earlier neurofibrillary tangle (NFT) accumulation in specific brain regions (I-II) compared to later regions (III-VI), aligning with Alzheimer's disease (AD) amyloid-beta (Aβ) progression models.

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Genetics

Background:

  • Individuals with Down syndrome (DS) exhibit accelerated Alzheimer's disease (AD) pathology.
  • Previous studies utilized [11C]PiB PET for beta-amyloid (Aβ) and [18F]flortaucipir for neurofibrillary tangles (NFT).
  • This study extends analysis to a larger DS cohort using [18F]florbetapir for Aβ imaging.

Purpose of the Study:

  • To investigate the temporal relationship between regional NFT burden and a standardized model of Aβ onset in the DS population.
  • To determine the timing of NFT accumulation relative to Aβ progression in DS.
  • To identify specific Braak-associated regions with early NFT changes.

Main Methods:

  • Utilized longitudinal NFT and Aβ PET imaging in 282 participants with DS.
  • Employed Centiloid (CL) processing for Aβ scans and calculated standardized uptake value ratio (SUVR) for NFT regions.
  • Applied a generalized model for amyloid progression and aligned individual trajectories to estimate Aβ chronicity, fitting NFT SUVR and % Change to a linear mixed effects model.

Main Results:

  • Participants with dementia showed the highest NFT SUVR and latest Aβ chronicity, followed by Mild Cognitive Impairment (MCI).
  • NFT regions I-II demonstrated significantly increased SUVR within 0-5 years of Aβ onset, while regions III-VI showed increases at 5-10 years.
  • NFT region I showed significant % Change increase within 0-5 years, whereas NFT regions III-VI showed increases after >10 years.

Conclusions:

  • NFT regions I-II exhibit earlier increases in [18F]flortaucipir SUVR compared to other NFT regions.
  • Findings support a standardized temporal model for Aβ onset in understanding NFT progression in DS.
  • Age, sex, scanner type, APOE4 status, and cognitive status significantly influenced NFT accumulation.