Dataset Information

Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study.

ABSTRACT: Introduction: The Down syndrome population has a high prevalence for dementia, often showing their first clinical symptoms in their 40s. Methods: In a longitudinal cohort, we investigate whether amyloid deposition at time point 1 (TP1) could predict cortical thickness change at time point 2 (TP2). The association between tau burden and cortical thickness was also examined at time point 3 (TP3). Results: Between TP1 and TP2 there was pronounced cortical thinning in temporo-parietal cortices and cortical thickening in the frontal cortex. Baseline amyloid burden was strongly associated to cortical thinning progression, especially in the temporo-parietal regions. At TP3, tau deposition negatively correlated with cortical atrophy in regions where tau usually accumulates at later Braak stages. Discussion: A higher amount of amyloid accumulation triggers a cascade of changes of disease-causing processes that eventually lead to dementia. As expected, we found that regions where tau usually accumulates were those also displaying high levels of cortical atrophy.

SUBMITTER: Padilla C

PROVIDER: S-EPMC8974205 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study.

Padilla Concepcion C Montal Victor V Walpert Madeleine J MJ Hong Young T YT Fryer Tim D TD Coles Jonathan P JP Aigbirhio Franklin I FI Hartley Sigan L SL Cohen Ann D AD Tudorascu Dana L DL Christian Bradley T BT Handen Benjamin L BL Klunk William E WE Holland Anthony J AJ Zaman Shahid H SH

Alzheimer's & dementia (Amsterdam, Netherlands) 20220401 1

Introduction: The Down syndrome population has a high prevalence for dementia, often showing their first clinical symptoms in their 40s. Methods: In a longitudinal cohort, we investigate whether amyloid deposition at time point 1 (TP1) could predict cortical thickness change at time point 2 (TP2). The association between tau burden and cortical thickness was also examined at time point 3 (TP3). Results: Between TP1 and TP2 there was pronounced cortical thinning in temporo-pa ...[more]

PMID: 35386472

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Project description:BackgroundThe aim of this longitudinal study was to assess with positron emission tomography (PET) the relationship between levels of inflammation and the loads of aggregated β-amyloid and tau at baseline and again after 2 years in prodromal Alzheimer's disease.MethodsForty-three subjects with mild cognitive impairment (MCI) had serial 11C-PK11195 PET over 2 years to measure inflammation changes, and 11C-PiB PET to determine β-amyloid fibril load; 22 also had serial 18F-Flortaucipir PET to determine tau tangle load. Cortical surface statistical mapping was used to localise areas showing significant changes in tracer binding over time and to interrogate correlations between tracer binding of the tracers at baseline and after 2 years.ResultsThose MCI subjects with high 11C-PiB uptake at baseline (classified as prodromal Alzheimer's disease) had raised inflammation levels which significantly declined across cortical regions over 2 years although their β-amyloid levels continued to rise. Those MCI cases who had low/normal 11C-PiB uptake at baseline but their levels then rose over 2 years were classified as prodromal AD with low Thal phase 1-2 amyloid deposition at baseline. They showed levels of cortical inflammation which correlated with their rising β-amyloid load. Those MCI cases with baseline low 11C-PiB uptake that remained stable were classified as non-AD, and they showed no correlated inflammation levels. Finally, MCI cases which showed both high 11C-PiB and 18F-Flortaucipir uptake at baseline (MCI due to AD) showed a further rise in their tau tangle load over 2 years with a correlated rise in levels of inflammation.ConclusionsOur baseline and 2-year imaging findings are compatible with a biphasic trajectory of inflammation in Alzheimer's disease: MCI cases with low baseline but subsequently rising β-amyloid load show correlated levels of microglial activation which then later decline when the β-amyloid load approaches AD levels. Later, as tau tangles form in β-amyloid positive MCI cases with prodromal AD, the rising tau load is associated with higher levels of inflammation.

Project description:Heterogeneity within the Alzheimer's disease (AD) syndromic spectrum is typically classified in a domain-specific manner (e.g., language vs. visual cognitive function). The central aim of this study was to investigate whether impairment in visual cognitive tasks thought to be subserved by posterior cortical dysfunction in non-amnestic AD presentations is associated with tau, amyloid, or neurodegeneration in those regions using 18F-AV-1451 and 11C-PiB positron emission tomography (PET) and magnetic resonance imaging (MRI). Sixteen amyloid-positive patients who met criteria for either Posterior Cortical Atrophy (PCA; n = 10) or logopenic variant Primary Progressive Aphasia (lvPPA; n = 6) were studied. All participants underwent a structured clinical assessment, neuropsychological battery, structural MRI, amyloid PET, and tau PET. The neuropsychological battery included two visual cognitive tests: VOSP Number Location and Benton Facial Recognition. Surface-based whole-cortical general linear models were used to first explore the similarities and differences between these biomarkers in the two patient groups, and then to assess their regional associations with visual cognitive test performance. The results show that these two variants of AD have both dissociable and overlapping areas of tau and atrophy, but amyloid is distributed with a stereotyped localization in both variants. Performance on both visual cognitive tests were associated with tau and atrophy in the right lateral and medial occipital association cortex, superior parietal cortex, and posterior ventral occipitotemporal cortex. No cortical associations were observed with amyloid PET. We further demonstrate that cortical atrophy has a partially mediating effect on the association between tau pathology and visual cognitive task performance. Our findings show that non-amnestic variants of AD have partially dissociable spatial patterns of tau and atrophy that localize as expected based on symptoms, but similar patterns of amyloid. Further, we demonstrate that impairments of visual cognitive dysfunction are strongly associated with tau in visual cortical regions and mediated in part by atrophy.

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Dataset Information

Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study.

Publications

Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study.

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