Ante mortem amyloid imaging and β-amyloid pathology in a case with dementia with Lewy bodies

Abstract

The association between antemortem [ 11 C]-Pittsburgh Compound B (PiB) retention and β-amyloid (Aβ) load, Lewy body (LB) and neurofibrillary tangle (NFT) densities were investigated in a pathologically confirmed case of dementia with LB (DLB). 76-year-old man presenting with a clinical diagnosis of DLB had undergone PiB-positron emission tomography (PET), 18 F FDG-PET and MRI 18 months before death. The pathologic diagnosis was DLB neocortical-type with low-likelihood of Alzheimer's disease by NIA-Reagan criteria. Sections from regions of interest (ROI) on post-mortem examination were studied. A significant correlation was found between cortical Aβ density and PiB retention in the 17 corresponding ROIs (r=0.899; p<0.0001). Bielschowsky silver stain revealed mostly sparse neocortical neuritic plaques; whereas diffuse plaques were frequent. There was no correlation between LB density and PiB retention (r=0.13; p=0.66); nor between NFT density and PiB retention (r=−0.36; p=0.17). The ROI-based analysis of imaging and histopathological data confirms that PiB uptake on PET is a specific marker for Aβ density, but cannot differentiate neuritic from diffuse amyloid plaques in this case with DLB.

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

“…The relationship between disease progression and PiB may be suggestive of a more complex relationship between amyloid-b, tau and -synuclein that is not easily disentangled by examining only amyloid-b. Furthermore, since PiB imaging does not distinguish between amyloid-b deposition of diffuse more than neuritic plaques (Kantarci et al, 2012c), it is also not known whether this distinction may make a difference in the effects of amyloid protein aggregation in DLB, and may contribute to some of this variability. Overall our findings are in agreement with the hypothesis that patients with probable DLB with concomitant underlying Alzheimer's disease pathology could show a more aggressive clinical phenotype of the disease with increased atrophy rates and functional decline (Nelson et al, 2009;Clinton et al, 2010;Gomperts et al, 2012;De Beer et al, 2015;Ferman et al, 2015;Graff-Radford et al, 2015;Howlett et al, 2015).…”

“…Future studies that include ante-mortem imaging and post-mortem pathological analysis, as well as bigger sample sizes are needed to better understand PiB retention as a surrogate marker of amyloid-b deposition in DLB (Kantarci et al, 2012c).…”

“…Amyloid PET labelling tracer 11 C-Pittsburgh compound B (PiB) is an in vivo biomarker of amyloid-b deposition in DLB (Fodero-Tavoletti et al, 2007;Burack et al, 2010;Driscoll et al, 2012;Kantarci et al, 2012c). Meta-analysis from multiple cohorts indicates that 68% of patients with probable DLB have abnormal PiB retention (Petrou et al, 2015).…”

Dementia with Lewy bodies

“…PiB positivity may not always point to high likelihood of AD because a positive PiB-PET scan has been observed in patients with Lewy body disease who had frequent diffuse plaques but sparse neuritic plaques and low to intermediate Braak NFT stage, which would classify them as having high likelihood of DLB. 25 Therefore, additional information from the CIS may be useful.…”

Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease

“…However, they are not approved for positive diagnosis of AD; rather, they are recommended for excluding the likelihood of AD. The fundamental limitation of these three tracers and others under development is that they bind primarily to insoluble Aβs, not the more toxic soluble Aβs (26)(27)(28)(29)(30)(31)(32). Clearly, work remains to be done Significance Drug development for Alzheimer's disease (AD) has been largely unsuccessful to date.…”