The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis

Abstract

People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.

Keywords: Alzheimer's disease; Amyloid; Cortical thickness; Down syndrome; Gray matter volume.

Fig. 1

The cortical signature of the Down syndrome brain without amyloid pathology: regional variations in cortical thickness across the hemispheres in the PIB-negative group (n = 27) in comparison to control group (n = 30). The color scale on the right represents the significance of the thickness difference as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-negative group relative to controls. The results are false discovery rate corrected at p < 0.05.

Fig. 2

The cortical signature of the Down syndrome brain with amyloid pathology: regional variations in cortical thickness in the PIB-positive group (n = 19), when compared to PIB-negative group (n = 27). The color scale on the right represents the significance of the difference in thickness as −log 10 (p-value) with red-yellow indicating thinner cortex and blue-light blue indicating thicker cortex in the PIB-positive group relative to PIB-negative group. The results are false discovery rate corrected at p < 0.05.

Fig. 3

Volumes of the deep gray matter structures and total brain in the control, PIB-negative and PIB-positive groups. Unfilled circles in the PIB-positive group represent the 3 individuals who had too advanced dementia to be able to perform the CAMCOG cognitive assessment. ^∗p < 0.05, ^∗∗∗p < 0.001, NS, nonsignificant. All tests are 2-sample t-test results (2-tailed) following a 1-way analysis of variance. Abbreviation: CAMCOG, Cambridge Examination for Mental Disorders in Older people with DS and others with Intellectual Disabilities.