Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.

We present a new application of positron emission tomography ("ntPET" or "neurotransmitter PET") designed to recover temporal patterns of neurotransmitter release from dynamic data. Our approach employs an enhanced tracer kinetic model that describes uptake of a labeled dopamine D2/D3 receptor ligand in the presence of a time-varying rise and fall in endogenous dopamine. Data must be acquired during both baseline and stimulus (transient dopamine release) conditions. Data from a reference region in both conditions are used as an input function, which alleviates the need for any arterial blood sampling. We use simulation studies to demonstrate the ability of the method to recover the temporal characteristics of an increase in dopamine concentration that might be expected following a drug treatment. The accuracy and precision of the method-as well as its potential for false-positive responses due to noise or changes in blood flow-were examined. Finally, we applied the ntPET method to small-animal imaging data in order to produce the first noninvasive assay of the time-varying release of dopamine in the rat striatum following alcohol.

The results of this study support the hypothesis that there are abnormalities in the dopaminergic system in BPD, and suggest that DAT availability may be related to the neuropathology of BPD. Future studies are needed to determine if DAT availability cycles with disease phase.

Service-learning has become an important component of higher education. Integrating service-learning into dental and dental hygiene curricula will foster graduates who are better prepared to work effectively among diverse populations and to function dynamically in the health policy arena. Although the phrase is familiar to dental educators, there is not a consistent understanding of what comprises this pedagogy. This article offers a framework for service-learning in dental education and describes ten components that characterize true service-learning. This framework can provide a common understanding of this form of experiential education that brings community engagement and educational objectives together. More effective programs can be built around a shared understanding of the characteristics and goals of service-learning in dental education.

Striatal dopamine (DA) is increased by virtually all drugs of abuse, including alcohol. However, drug-associated cues are also known to provoke striatal DA transmission-a phenomenon linked to the motivated behaviors associated with addiction. To our knowledge, no one has tested if alcohol's classically conditioned flavor cues, in the absence of a significant pharmacologic effect, are capable of eliciting striatal DA release in humans. Employing positron emission tomography (PET), we hypothesized that beer's flavor alone can reduce the binding potential (BP) of [ 11 C]raclopride (RAC; a reflection of striatal DA release) in the ventral striatum, relative to an appetitive flavor control. Forty-nine men, ranging from social to heavy drinking, mean age 25, with a varied family history of alcoholism underwent two [ 11 C]RAC PET scans: one while tasting beer, and one while tasting Gatorade. Relative to the control flavor of Gatorade, beer flavor significantly increased self-reported desire to drink, and reduced [ 11 C]RAC BP, indicating that the alcohol-associated flavor cues induced DA release. BP reductions were strongest in subjects with first-degree alcoholic relatives. These results demonstrate that alcoholconditioned flavor cues can provoke ventral striatal DA release, absent significant pharmacologic effects, and that the response is strongest in subjects with a greater genetic risk for alcoholism. Striatal DA responses to salient alcohol cues may thus be an inherited risk factor for alcoholism.

IntroductionPathophysiological changes that accompany early clinical symptoms in prodromal Alzheimer's disease (AD) may have a disruptive influence on brain networks. We investigated resting-state functional magnetic resonance imaging (rsfMRI), combined with brain connectomics, to assess changes in whole-brain functional connectivity (FC) in relation to neurocognitive variables.MethodsParticipants included 58 older adults who underwent rsfMRI. Individual FC matrices were computed based on a 278-region parcellation. FastICA decomposition was performed on a matrix combining all subjects' FC. Each FC pattern was then used as a response in a multilinear regression model including neurocognitive variables associated with AD (cognitive complaint index [CCI] scores from self and informant, an episodic memory score, and an executive function score).ResultsThree connectivity independent component analysis (connICA) components (RSN, VIS, and FP-DMN FC patterns) associated with neurocognitive variables were identified based on prespecified criteria. RSN-pattern, characterized by increased FC within all resting-state networks, was negatively associated with self CCI. VIS-pattern, characterized by an increase in visual resting-state network, was negatively associated with CCI self or informant scores. FP-DMN-pattern, characterized by an increased interaction of frontoparietal and default mode networks (DMN), was positively associated with verbal episodic memory.DiscussionSpecific patterns of FC were differently associated with neurocognitive variables thought to change early in the course of AD. An integrative connectomics approach relating cognition to changes in FC may help identify preclinical and early prodromal stages of AD and help elucidate the complex relationship between subjective and objective indices of cognitive decline and differences in brain functional organization.

The heterogeneity of dopaminergic responses to alcohol across subjects may be a reason for the lack of reports demonstrating DA involvement in alcohol-related behaviors. By allowing for different spatial patterns of DA release within each subject's striata, we showed correlations between alcohol-induced DA release in the striata and behavioral outcomes related to alcohol.

Resting D2 receptor availability may predict healthy subject responses to alcohol exposure.