Amyloid-β (Aβ) plaque deposition can precede the clinical manifestations of dementia of the Alzheimer type (DAT) by many years and can be associated with changes in brain metabolism. Both the Aβ plaque deposition and the changes in metabolism appear to be concentrated in the brain's default-mode network. In contrast to prior studies of brain metabolism which viewed brain metabolism from a unitary perspective that equated glucose utilization with oxygen consumption, we here report on regional glucose use apart from that entering oxidative phosphorylation (so-called “aerobic glycolysis”). Using PET, we found that the spatial distribution of aerobic glycolysis in normal young adults correlates spatially with Aβ deposition in individuals with DAT and cognitively normal participants with elevated Aβ, suggesting a possible link between regional aerobic glycolysis in young adulthood and later development of Alzheimer pathology.

Alzheimer9s disease (AD) pathology is estimated to develop many years before detectable cognitive decline. Fluid and imaging biomarkers may identify people in early symptomatic and even preclinical stages, possibly when potential treatments can best preserve cognitive function. We previously reported that cerebrospinal fluid (CSF) levels of amyloid‐β₄₂ (Aβ₄₂) serve as an excellent marker for brain amyloid as detected by the amyloid tracer, Pittsburgh compound B (PIB). Using data from 189 cognitively normal participants, we now report a positive linear relationship between CSF tau/ptau₁₈₁ (primary constituents of neurofibrillary tangles) with the amount of cortical amyloid. We observe a strong inverse relationship of cortical PIB binding with CSF Aβ₄₂ but not for plasma Aβ species. Some individuals have low CSF Aβ₄₂ but no cortical PIB binding. Together, these data suggest that changes in brain Aβ₄₂ metabolism and amyloid formation are early pathogenic events in AD, and that significant disruptions in CSF tau metabolism likely occur after Aβ₄₂ initially aggregates and increases as amyloid accumulates. These findings have important implications for preclinical AD diagnosis and treatment.

The sigma-2 receptor, whose gene remains to be cloned, has been validated as a biomarker for tumour cell proliferation. Here we report the use of a novel photoaffinity probe, WC-21 , to identify the sigma-2 receptor-binding site. WC-21 , a sigma-2 ligand containing both a photoactive azide moiety and a fluorescein isothiocyanate group, irreversibly labels sigma-2 receptors in rat liver; the membrane-bound protein was identified as PGRMC1 (progesterone receptor membrane component 1). Immunocytochemistry reveals that both PGRMC1 and SW120 , a fluorescent sigma-2 receptor ligand, colocalize with molecular markers of the endoplasmic reticulum and mitochondria in HeLa cells. Overexpression and knockdown of the PGRMC1 protein results in an increase and a decrease in binding of a sigma-2 selective radioligand, respectively. The identification of the putative sigma-2 receptor-binding site as PGRMC1 should stimulate the development of unique imaging agents and cancer therapeutics that target the sigma-2 receptor/PGRMC1 complex.

Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the emergence of 'self-invented' terms. In order to address these concerns, an international Working Group on 'Nomenclature in Radiopharmaceutical Chemistry and related areas' was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field. Upon open consultation, the following consensus guidelines were agreed, which aim to.