Down syndrome: Age-dependence of PiB binding in postmortem frontal cortex across the lifespan

Publication date: Available online 14 March 2017
Source:Neurobiology of Aging
Author(s): Harry LeVine, H. Peter Spielmann, Sergey Matveev, Francesca Macchiavello Cauvi, M. Paul Murphy, Tina L. Beckett, Katie McCarty, Ira T. Lott, Eric Doran, Frederick Schmitt, Elizabeth Head
Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro ³H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, ³H-PiB binding was significantly associated with age. After age 40 years in DS, ³H-PiB binding rose dramatically along with increasing individual variability. ³H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy (CAA) showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and CAA in DS brain.



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