Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Structural MRI across lifespan reveals differential thalamic trajectories in Down syndrome.
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Shaikh Muhammad, Fletcher Paul, Zaman Shahid, Alzheimer's Biomarker Consortium on Down Syndrome, Brown Stephanie
Аннотация
INTRODUCTION: Up to 90% of Down syndrome (DS) patients develop Alzheimer's disease (AD). Sleep disturbance, affecting over 75% of DS patients, is implicated in AD pathogenesis. The thalamus, central to sleep and arousal, shows early vulnerability in DS-related AD.
METHODS: Structural 3T MRI scans from 253 DS participants (119 males, mean age 43.0 ± 9.4 years) and 36 controls (30 males, mean age 43.1 ± 12.2 years) from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study were analyzed, alongside neurodegenerative plasma biomarker assays (phosphorylated tau [pTau]181, pTau217, neurofilament light chain [NfL], amyloid beta [Aβ]40, Aβ42).
RESULTS: In DS, intracranial volume-adjusted thalamic volume declined with age (t = -2.589, p = 0.00987), approximating 2.5% loss per decade. This was linear, gray matter involution-independent, and heterogeneous across nuclei, correlating negatively with pTau and NfL. Controls exhibited no significant volumetric changes.
DISCUSSION: Anteromedial and posterior thalamic shrinkage in DS AD mirrors sporadic AD. Associations with neurodegenerative biomarkers support thalamic atrophy as a sensitive marker of DS-related AD progression.
METHODS: Structural 3T MRI scans from 253 DS participants (119 males, mean age 43.0 ± 9.4 years) and 36 controls (30 males, mean age 43.1 ± 12.2 years) from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study were analyzed, alongside neurodegenerative plasma biomarker assays (phosphorylated tau [pTau]181, pTau217, neurofilament light chain [NfL], amyloid beta [Aβ]40, Aβ42).
RESULTS: In DS, intracranial volume-adjusted thalamic volume declined with age (t = -2.589, p = 0.00987), approximating 2.5% loss per decade. This was linear, gray matter involution-independent, and heterogeneous across nuclei, correlating negatively with pTau and NfL. Controls exhibited no significant volumetric changes.
DISCUSSION: Anteromedial and posterior thalamic shrinkage in DS AD mirrors sporadic AD. Associations with neurodegenerative biomarkers support thalamic atrophy as a sensitive marker of DS-related AD progression.