Abstract In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. We used Positron Emission Tomography with a radiotracer sensitive to the TSPO molecule expressed by activated microglia to assess, for the first time, human hypothalamic inflammation. We found that women but not men showed age-correlated hypothalamic TSPO expression, and suggest this is relevant to understanding a stark sex difference in human aging, namely, that only women undergo menopause.

In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23–78), focusing on hypothalamus. We found robust age-correlated TSPO expression in thalamus but not hypothalamus in the combined group of women and men. This pattern differs from what has been described in rodents. Prominent age-correlated TSPO expression in thalamus in humans, but in hypothalamus in rodents, could reflect evolutionary changes in size and function of thalamus versus hypothalamus, and may be relevant to the appropriateness of using rodents to model human aging. When examining TSPO PET results in women and men separately, we found that only women showed age-correlated hypothalamic TSPO expression. We suggest this novel result is relevant to understanding a stark sex difference in human aging: that only women undergo loss of fertility—menopause—at mid-life. Our finding of age-correlated hypothalamic inflammation in women could have implications for understanding and perhaps altering reproductive aging in women.

Repeated mild Traumatic Brain Injury (TBI) is a risk factor for Chronic Traumatic Encephalopathy (CTE), characterized pathologically by neurofibrillary tau deposition in the depths of brain sulci and surrounding blood vessels. The mechanism by which TBI leads to CTE remains unknown but has been posited to relate to axonal shear injury leading to release and possibly deposition of tau at the time of injury. As part of an IRB-approved study designed to learn how processes occurring acutely after TBI may predict later proteinopathy and neurodegeneration, we performed tau PET using 18F-MK6240 and MRI within 14 days of complicated mild TBI in three subjects. PET radiotracer accumulation was apparent in regions of traumatic hemorrhage in all subjects, with prominent intraparenchymal PET signal in one young subject with a history of repeated sports-related concussions. These results are consistent with off-target tracer binding to blood products as well as possible on-target binding to chronically and/or acutely-deposited neurofibrillary tau. Both explanations are highly relevant to applying tau PET to understanding TBI and CTE. Additional study is needed to assess the potential utility of tau PET in understanding how processes occurring acutely after TBI, such as release and deposition of tau and blood from damaged axons and blood vessels, may relate to development CTE years later.

SummaryIn animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure‐free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy.

The neurobiology of anorexia nervosa remains incompletely understood. Here we utilized PET imaging with the radiotracer [C-11]raclopricle to measure striatal dopamine type 2 (D-2) receptor availability in patients with anorexia nervosa. 25 women with anorexia nervosa who were receiving treatment in an inpatient program participated, as well as 25 control subjects. Patients were scanned up to two times with the PET tracer [C-11]raclopricle: once while underweight, and once upon weight restoration. Control subjects underwent one PET scan. In the primary analyses, there were no significant differences between underweight: patients (n=21) and control subjects (n =25) in striatal D-2 receptor binding potential. Analysis of subregions (sensorimotor striatum, associative striatum, limbic striatum) did not reveal differences between groups. In patients completing both scans (n 15) there were no detectable changes in striatal D-2 receptor binding potential after weight restoration. In this sample, there were no differences in striatal D-2 receptor binding potential between patients with anorexia nervosa and control subjects. Weight restoration was not associated with a change in striatal D2 receptor binding. These findings suggest that disturbances in reward processing in this disorder are not attributable to abnormal D2 receptor characteristics, and that other reward related neural targets may be of greater relevance. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

192 Objectives: Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder characterized by gradually deteriorating expressive language function and variable progression to a more generalized dementia. There is currently no antemortem method to distinguish cases of PNFA related to Alzheimer’s from those caused by other disorders. In an effort to make this distinction, we examined whether PET imaging using the Pittsburgh Compound B, [11C]PIB revealed distinctive patterns of amyloid deposition in clinically diagnosed PNFA versus AD. Methods: Three patients with a clinical diagnosis of PNFA and three age- and gender-matched patients with mild probable AD were included in this study. All subjects underwent FDG-PET, PIB-PET and CT scans under an IRB-approved protocol. With both tracers, venous samples were used to generate blood time activity curves. Quantitative cerebral glucose utilization images were derived from the FDG scans and blood data. Modified Logan plots were generated with cerebellar references for the analysis of the PIB scans. Results: All subjects showed decreased cerebral metabolism, but in two PNFA patients hypometabolism was asymmetric with accentuated left-sided abnormalities in language-related cortical regions. All PNFA patients demonstrated bilateral cortical PIB retention, but the two patients with asymmetric FDG hypometabolism retained PIB to lesser degree. The one PNFA patient who progressed to a more generalized dementia showed FDG and PIB activity patterns similar to that of AD. Conclusions: The asymmetric distribution of PIB and lateralized cerebral hypometabolism observed in patients with PNFA may be useful in identifying this entity. The finding of PIB retention in all three PNFA subjects was unexpected given the lack of plaque pathology in as many as 2/3 of PNFA patients who have come to autopsy. This could reflect underlying AD pathology in these three cases, or binding of PIB to fibrillar proteins other than beta amyloid. Further studies of PIB binding in other PNFA cases are therefore warranted.