E.M. designed the study and wrote the initial draft of the manuscript. All authors collected samples and data, helped to interpret the results and reviewed drafts of the manuscript.Competing interests R.J.B. has equity ownership interest in C2N Diagnostics and receives royalty income based on technology (stable isotope labeling kinetics and blood plasma assay) licensed by Washington University to C2N Diagnostics. R.J.B. receives income from C2N Diagnostics for serving on the scientific advisory board. Washington University, with R.J.B., E.M. and N.R.B. as co-inventors, has submitted the US nonprovisional patent application 'Cerebrospinal fluid (CSF) tau rate of phosphorylation measurement to define stages of Alzheimer's disease and monitor brain kinases/phosphatases activity'. R.J.B. has received honoraria from Janssen and Pfizer as a speaker, and from Merck and Pfizer as an advisory board member. E.M. has received royalty payments for an educational program supported by Eli Lilly and as a member of a scientific advisory board for Eli Lilly.

Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

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Cerebral aging is often associated with the occurrence of neurodegenerative diseases leading to dementia. Animal models are critical to elucidate mechanisms associated to dementia and to evaluate neuroprotective drugs. Rats that received intracerebroventricular injection of streptozotocin (icv-STZ) have been reported as a model of dementia. In these animals, this drug induces oxidative stress and brain glucose metabolism impairments associated to insulin signal transduction failure. These mechanisms are reported to be involved in the pathogenesis of Alzheimer's disease and other dementia. Icv-STZ rats also display memory impairments. However, little is known about the precise location of the lesions induced by STZ administration. In this context, the present study characterized the cerebral lesions induced by two-doses of icv-STZ by using high-field magnetic resonance imaging to easily and longitudinally detect cerebral abnormalities and by using immunohistochemistry to evaluate neuronal loss and neuroinflammation (astrocytosis and microgliosis). We showed that, at high doses, icv-STZ induces severe and acute neurodegenerative lesions in the septum and corpus callosum. The lesions are associated with an inflammation process. They are less severe and more progressive at low doses. The relevance of high and low doses of icv-STZ to mimic dementia and evaluate new drugs is discussed in the final part of this article.