Contributions of sex and genotype to exploratory behavior differences in an aged humanized APOE mouse model of late-onset Alzheimer's disease.

Age, genetics, and chromosomal sex have been identified as critical risk factors for late-onset Alzheimer's disease (LOAD). The predominant genetic risk factor for LOAD is the apolipoprotein E ε4 allele (APOE4), and the prevalence of LOAD is higher in females. However, the translational validity of APOE4 mouse models for AD-related cognitive impairment remains to be fully determined. The present study investigated the role of both sex and genotype on learning and memory in aged, humanized APOE knock-in mice. Aged (23.27 mo ± 1.21 mo; 39 male/37 female) APOE3/3, APOE3/4, and APOE4/4 mice performed a novel object recognition (NOR) assay. Task-related metrics were analyzed using two-way sex by genotype ANOVAs. Sex differences were more prominent relative to APOE genotype. Prior to NOR, female mice exhibited thigmotaxic center zone avoidance during the open field task relative to males, regardless of genotype. Within object familiarization and NOR tasks, females had greater object interaction and locomotion. Interestingly, only APOE4/4 females on average recognized the novel object. These results suggest that APOE4, although strongly related to LOAD pathogenesis, does not drive cognitive decline in the absence of other risk factors even in very aged mice. Chromosomal sex is a key driver of behavioral phenotypes and thus is a critical variable for translatability of interventions designed to preserve learning and memory in animal models of LOAD. Last, there was a very high degree of variability in behavioral performance across APOE genotypes. A cluster analysis of the behavioral data revealed a low-activity and a high-activity cluster. APOE4 carriers were overrepresented in the low-activity cluster, while male:female distributions did not differ. Collectively, the behavioral data indicate that chromosomal sex has the greatest impact on behavioral phenotype, and APOE4 carrier status may confer greater risk for cognitive decline in some animals.

Mild cognitive impairment and structural brain abnormalities in a sexagenarian with a history of childhood traumatic brain injury.

In this report, we present a case study involving an older, female patient with a history of pediatric traumatic brain injury (TBI). Magnetic resonance imaging and diffusion tensor imaging volumes were acquired from the volunteer in question, her brain volumetrics and morphometrics were extracted, and these were then systematically compared against corresponding metrics obtained from a large sample of older healthy control (HC) subjects as well as from subjects in various stages of mild cognitive impairment (MCI) and Alzheimer disease (AD). Our analyses find the patient's brain morphometry and connectivity most similar to those of patients classified as having early-onset MCI, in contrast to HC, late MCI, and AD samples. Our examination will be of particular interest to those interested in assessing the clinical course in older patients having suffered TBI earlier in life, in contradistinction to those who experience incidents of head injury during aging.

Neuroimaging of traumatic brain injury in military personnel: An overview.

BACKGROUND: The incidence of blunt-force traumatic brain injury (TBI) is especially prevalent in the military, where the emergency care admission rate has been reported to be 24.6-41.8 per 10,000 soldier-years. Given substantial advancements in modern neuroimaging techniques over the past decade in terms of structural, functional, and connectomic approaches, this mode of exploration can be viewed as best suited for understanding the underlying pathology and for providing proper intervention at effective time-points. APPROACH: Here we survey neuroimaging studies of mild-to-severe TBI in military veterans with the intent to aid the field in the creation of a roadmap for clinicians and researchers whose aim is to understand TBI progression. DISCUSSION: Recent advancements on the quantification of neurocognitive dysfunction, cellular dysfunction, intracranial pressure, cerebral blood flow, inflammation, post-traumatic neuropathophysiology, on blood serum biomarkers and on their correlation to neuroimaging findings are reviewed to hypothesize how they can be used in conjunction with one another. This may allow clinicians and scientists to comprehensively study TBI in military service members, leading to new treatment strategies for both currently-serving as well as veteran personnel, and to improve the study of TBI more broadly.

Democratizing data science through data science training.

The biomedical sciences have experienced an explosion of data which promises to overwhelm many current practitioners. Without easy access to data science training resources, biomedical researchers may find themselves unable to wrangle their own datasets. In 2014, to address the challenges posed such a data onslaught, the National Institutes of Health (NIH) launched the Big Data to Knowledge (BD2K) initiative. To this end, the BD2K Training Coordinating Center (TCC; bigdatau.org) was funded to facilitate both in-person and online learning, and open up the concepts of data science to the widest possible audience. Here, we describe the activities of the BD2K TCC and its focus on the construction of the Educational Resource Discovery Index (ERuDIte), which identifies, collects, describes, and organizes online data science materials from BD2K awardees, open online courses, and videos from scientific lectures and tutorials. ERuDIte now indexes over 9,500 resources. Given the richness of online training materials and the constant evolution of biomedical data science, computational methods applying information retrieval, natural language processing, and machine learning techniques are required - in effect, using data science to inform training in data science. In so doing, the TCC seeks to democratize novel insights and discoveries brought forth via large-scale data science training.

Multimodal Imaging of Neurometabolic Pathology due to Traumatic Brain Injury.

The impact of traumatic brain injury (TBI) involves a combination of complex biochemical processes beginning with the initial insult and lasting for days, months and even years post-trauma. These changes range from neuronal integrity losses to neurotransmitter imbalance and metabolite dysregulation, leading to the release of pro- or anti-apoptotic factors which mediate cell survival or death. Such dynamic processes affecting the brain's neurochemistry can be monitored using a variety of neuroimaging techniques, whose combined use can be particularly useful for understanding patient-specific clinical trajectories. Here, we describe how TBI changes the metabolism of essential neurochemical compounds, summarize how neuroimaging approaches facilitate the study of such alterations, and highlight promising ways in which neuroimaging can be used to investigate post-TBI changes in neurometabolism.