Early striatal amyloid deposition distinguishes Down syndrome and autosomal dominant Alzheimer's disease from late-onset amyloid deposition

Abstract

Introduction: The objective of this study was to evaluate amyloid β (Aβ) deposition patterns in different groups of cerebral β amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Aβ clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Aβ clearance (preclinical AD).

Methods: We performed whole-brain voxelwise comparison of cerebral Aβ between 23 Down syndrome, 10 preclinical autosomal dominant Alzheimer disease, 17 late-onset AD, and 16 preclinical AD subjects, using Pittsburgh Compound B-positron emission tomography.

Results: We found both Down syndrome and preclinical autosomal dominant Alzheimer disease shared a distinct pattern of increased bilateral striatal and thalamic Aβ deposition compared to late-onset AD and preclinical AD.

Conclusion: Disorders associated with early-life alterations in amyloid precursor protein production or processing are associated with a distinct pattern of early striatal fibrillary Aβ deposition before significant cognitive impairment. A better understanding of this unique pattern could identify important mechanisms of Aβ deposition and possibly important targets for early intervention.

Keywords: Autosomal dominant Alzheimer dementia; Aβ42; Diffuse plaque; Down syndrome; Pittsburgh compound B; Striatum.

Figure 1

Voxelwise Comparison of Amyloid Patterns between ADAD, DS and LOAD. p-values FDR-corrected (p<0.05). Color bar represents t-values.

Figure 2

Linear regression plots for each ROI vs. the average cortical ROI.