For a given (Aβ) burden, individuals with (DS) exhibited greater burden than neurotypical aging.
Cognitively stable DS individuals show higher tau levels compared to neurotypical individuals at similar Aβ levels.
DS individuals with mild cognitive impairment or Alzheimer's disease display more widespread tau pathology.
Aβ-associated tau burden is linked to episodic memory impairment in DS before dementia onset.
Executive dysfunction becomes evident as Alzheimer's disease progresses in individuals with DS.
Early striatal Aβ accumulation in DS may serve as a potential biomarker for monitoring disease progression.
Simplified
INTRODUCTION: Individuals with (DS) have elevated risks for Alzheimer's disease (AD) due to (Aβ) precursor protein overexpression, with nearly all developing AD pathology by age 40 at autopsy. This study examined spatial associations between Aβ and burden in DS and neurotypical aging.
METHODS: Data included 145 DS (25-67 years) and 191 neurotypical aging individuals (63-89 years). Regional Aβ and tau positron emission tomography outcomes were analyzed using multiset canonical correlation analysis to identify joint Aβ/tau spatial patterns, with regression models assessing associations with age and cognition.
RESULTS: For a given Aβ burden, cognitively stable DS individuals exhibited relatively higher tau burden than neurotypical aging, while DS mild cognitive impairment/AD individuals exhibited more widespread pathology. Joint Aβ/tau patterns were associated with episodic memory impairment in DS and, as the disease progresses, executive dysfunction.
DISCUSSION: DS exhibits overlapping and distinct AD-related neuropathology features, emphasizing the importance of biomarkers for early detection and intervention.
HIGHLIGHTS: There are distinct amyloid beta (Aβ) and tau spatial patterns in Down syndrome (DS): For a given level of Aβ burden, individuals with DS exhibited greater and more widespread tau burden compared to neurotypical aging, even before a clinical diagnosis of dementia. Aβ-associated tau burden was linked to episodic memory impairment in DS prior to dementia, with executive dysfunction emerging as the disease progressed, highlighting the sequential impact of pathology on cognition. The unique pattern of early striatal Aβ accumulation in DS supports its use as a potential biomarker for tracking disease progression and guiding clinical trial inclusion criteria for Alzheimer's disease interventions in DS.
Key numbers
27%
Higher Burden
Approximately 27% of individuals exhibited positive subject scores.
0.50
Cognitive Impairment Correlation
Higher expressions of the Aβ pattern were correlated significantly with age.
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