We will examine the available evidence for each of these assumptions in turn. Relationship between PET amyloid imaging and brain A?? burden by histopathology In vitro studies have shown that PET imaging ligands such as 11C-PIB [21,31], florbetaben [32] and florbetapir F 18 [24] bind to A?? and co-localize with plaques stained by thioflavin and other selleck chemicals Gemcitabine amyloid labeling agents. However, a definitive demonstration of the relationship requires a comparison between in vivo imaging and brain pathology, for example, at autopsy. Five single subject/single center PET to pathology comparison studies with 11C-PIB have produced mixed results. Two studies described patients with clinical diagnosis and autopsy confirmation of dementia with Lewy bodies (DLB) who had amyloid-positive 11C-PIB PET scans in life, and borderline A?? pathology at autopsy.

Bacskai and colleagues [33] reported a visually positive 11C-PIB PET scan from a 76 year old with DLB and severe cerebral amyloid angiopathy. Regional quantification of the PET image, expressed as distribution volume ratio (DVR), revealed low to moderately elevated tracer levels (DVR = 1.3 to 1.5), which was consistent with the autopsy findings of low to moderate levels of diffuse plaques and infrequent cored plaques (intermediate probability of AD by National Institute of Aging – Reagan Institute (NIA-Reagan) [34] criteria). However, there was no relationship across brain regions between regional DVR and regional levels of A??42 in autopsy tissue as assessed by ELISA. Kantarci and colleagues [35] reported a positive 11C-PIB PET scan from a 77 year old with DLB.

At autopsy neuritic plaques were moderately common in some brain regions, including mid-frontal gyrus, amygdale and superior Entinostat parietal lobe, but sparse in the areas used for pathological diagnosis, resulting in an NIA-Reagan classification of low likelihood AD. In contrast to the previous study, there was a strong correlation between regional quantification of the PET image and regional A?? density by immunohistochemistry at autopsy. Two other reports studied subjects with a clinical diagnosis of AD. Ikonomovic and colleagues [31] reported an amyloid positive 11C-PIB PET scan in a 64 year old with severe AD. Strong correlations (0.7 to 0.8) were seen between regional 11C-PIB PET tracer uptake (DVR) and various postmortem measures of A?? burden, including immunohistochemistry, histopathology phosphatase inhibitor and A?? levels by ELISA. Cairns and colleagues [36] reported on a 91 year old with clinical diagnosis of early AD with a negative 11C-PIB PET scan but reduced CSF A??.