Amyloid and tau deposition influences cognitive and functional decline in Down Syndrome

Abstract

AbstractBackgroundDown Syndrome (DS) is the most common neurodevelopmental disorder caused by the presence of trisomy 21 (1:800 to 1:1000 live births worldwide). The extra copy of chromosome 21 is associated with a 4‐5 fold overexpression of the amyloid precursor protein (APP) gene, increased accumulation of cerebral beta‐amyloid (Aβ) in the brain, subsequent neurofibrillary tangle (NFT) formation and neurodegeneration. This study investigates whether tau has (i) an independent effect from amyloid on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid in the exacerbation of decline in aging DS.Method105 participants with DS underwent baseline PET AV‐1451 and PET PiB scans to quantify tau deposition in Braak regions II‐VI and Striatum and amyloid‐β status respectively. A longitudinal cognitive testing battery was performed consistent with previous research in the same study cohort, with all participants completing at least two timepoints, and 26 completing three timepoints, with an average of 17 months between study visits. Linear Mixed Effects models were implemented to assess how tau and amyloid deposition are related to change over three time points.ResultThree cognitive outcome measures showed a significant effect of time: the Free + Cued Recall (t = ‐6.09, p < 0.01), Cued Intrusions (t = 3.19, p < 0.01) and NTG (z = 5.33, p = 0) variables. Tau SUVR was a significant independent predictor of cognitive and functional change. The three‐way interaction between time, PiB status and tau was significant in the models of episodic memory and visuospatial cognition (Figures 1‐3).ConclusionOur results contribute to an emerging framework in which the elevated risk of developing dementia involves mechanisms associated with both amyloid‐β and tau aggregation. This is supported by our finding that when including the two‐way interactions between amyloid status and time and regional tau and time in the same model, tau seems to be a more significant predictor of cognitive change over time than amyloid status. Our results suggest a synergistic relationship between PiB status and tau as predictors of change in memory and visuospatial cognition.