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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Funding for the current study was from the National Institutes of Health (NIH)/National Institutes of Child Health and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R01HD064993 (EH, FAS), NIH R21NS080576-01A1 (HL, HPS), BrightFocus A20140445 (HL) and NIH/National Institutes on Aging (NIA) P50AG16573, NIH/NIA R01AG21912 and NIH R01HD065160 (ITL, ED).
LeVine, Harry III; Spielmann, H. Peter; Matveev, Sergey V.; Cauvi, Francesca Macchiavello; Murphy, M. Paul; Beckett, Tina L.; McCarty, Katie; Lott, Ira T.; Doran, Eric; Schmitt, Frederick A.; and Head, Elizabeth, "Down Syndrome: Age-Dependence of PiB Binding in Postmortem Frontal Cortex Across the Lifespan" (2017). Sanders-Brown Center on Aging Faculty Publications. 123.