Abstract
BackgroundAutosomal dominant Alzheimer’s disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-β can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian Presenilin 1 E280A kindred.MethodsFourteen carriers (age = 28–42, Mini-Mental State Examination = 26–30) and 20 age-matched non-carriers were evaluated using PiB, flortaucipir (FTP; tau), and memory testing (CERAD Word List Learning). PiB-PET signal was measured in neocortical and striatal aggregates. FTP-PET signal was measured in entorhinal cortex.ResultsCompared to non-carriers, mutation carriers had age-related elevations in both neocortical and striatal PiB binding. The PiB elevation in carriers was significantly greater in the striatum than in the neocortex. In mutation carriers, PiB binding in both the neocortex and the striatum is related to entorhinal FTP; however, the association was stronger with the striatum. Only striatal PiB was associated with worse memory. Remarkably, PiB binding in the striatum, but not in the neocortex, predicted entorhinal FTP and lower memory scores after adjusting for age, indicating that striatal PiB identified the carriers with the most severe disease.ConclusionsBased on these preliminary cross-sectional findings, striatal PiB-PET measurements may offer particular value in the detection and tracking of preclinical ADAD, informing a mutation carrier’s prognosis and evaluating amyloid-β-modifying ADAD treatments.
Highlights
Autosomal dominant Alzheimer’s disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition
Because of this regional pattern, we examined whether a striatal Pittsburgh compound B (PiB) biomarker had different predictive value for disease severity, as assessed by tau-PET and memory performance, compared to the most commonly
Neocortical and striatal PiB-Distribution volume ratio (DVR) were higher in mutation carriers than in non-carriers (p < 0.0001)
Summary
Autosomal dominant Alzheimer’s disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-β deposition. Amyloid Pittsburgh compound B (PiB)-PET [5,6,7] and autopsy [5] data have raised the possibility that some forms of ADAD may be associated with greater fibrillar Aβ deposition in the striatum than the neocortex in the preclinical stages of ADAD, a pattern that is not typically observed in sporadic AD [8]. Because of this regional pattern, we examined whether a striatal PiB biomarker had different predictive value for disease severity, as assessed by tau-PET and memory performance, compared to the most commonly. Hanseeuw et al Alzheimer's Research & Therapy (2019) 11:17 used neocortical PiB biomarker, in cognitively unimpaired PSEN1-E280A mutation carriers and non-carriers from the largest known ADAD kindred due to a single-mutation
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