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Barrio, Jorge R.

Publications and source records attributed to Barrio, Jorge R..

7 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding

The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer’s disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. We examined the effect of TOMM40 and APOE on regional brain positron emission tomography (PET) 2-(1-{6-[(2 [F18]fluoroethyl) (methyl) amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) binding values in MTL.A total of 73 non-demented older adults (42 females; mean age: 62.9(10.9) completed genotyping for both APOE and TOMM40 and received FDDNP-PET scans. For TOMM40, the lengths of the poly-T sequence were classified as short (14–20 repeats; S), long (21–29 repeats, L) or very long (>29 repeats, VL). Using general linear models, we examined medial temporal lobe FDDNP binding and cognitive functioning between TOMM40 and APOE-4 groups, with age, sex, and education as covariates. Data from 30 individuals with APOE-4 and L TOMM40 poly-T length, 11 non E4 TOMM40 S/S, 14 non E4 TOMM40 S/VL and 13 non E4 TOMM40 VL/VL were analyzed. Medial temporal FDDNP binding differed significantly between TOMM40/APOE groups (F(3,62) = 3.3,p = .03). Participants with TOMM40 S/S exhibited significantly lower binding compared to TOMM40 S/VL and APOE-4 carriers. We did not find a significant relationship between TOMM40 poly-T lengths/APOE risk groups and cognitive functioning. This is the first report to demonstrate a significant association between longer TOMM40 poly-T lengths and higher medial temporal plaque and tangle burden in non-demented older adults. Identifying biomarkers that are risk factors for AD will enhance our ability to identify subjects likely to benefit from novel AD treatments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

In Vivo Brain Plaque and Tangle Burden Mediates the Association Between Diastolic Blood Pressure and Cognitive Functioning in Nondemented Adults

OBJECTIVE Growing evidence supports an association among increased blood pressure and: (a) poor cognitive performance in older adults, and (b) various biomarkers of increased Alzheimer's disease (AD) neuropathology. The objective of this study was to determine whether systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly associated with cognitive functioning in non-demented adults, and to examine in vivo AD pathology as a possible mediator of this association. METHODS Positron emission tomography (PET) scans with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) provide in vivo measurements of plaque and tangle burden. A total of 101 non-demented older subjects with blood pressure data and FDDNP-PET scans were drawn from a larger study of predictors of cognitive decline. A neuropsychological test battery was used to compute "global cognitive scores" (averaged across five key domains), which served as an index of general cognitive functioning. RESULTS Higher DBP (but not SBP) was significantly associated with lower cognitive scores, controlling for age, sex, antihypertensive medication use, and ApoE genotype (η2 = 0.06). However, this relationship was no longer significant after introducing FDDNP-PET binding as an additional covariate in the statistical models. In vivo plaque and tangle burden accounted for over 30% of the observed association between higher DBP and poorer cognitive performance. CONCLUSIONS By indicating a mediation of the relationship between DBP and cognitive functioning by FDDNP-PET binding, this study advances our understanding of some potential predictors of cognitive decline in non-demented adults, and underscores the importance of devising early multimodal interventions to more effectively combat degenerative brain disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Modular radiochemistry synthesis system

A modular chemical production system includes multiple modules for performing a chemical reaction, particularly of radiochemical compounds, from a remote location. One embodiment comprises a reaction vessel including a moveable heat source with the position thereof relative to the reaction vessel being controllable from a remote position. Alternatively the heat source may be fixed in location and the reaction vial is moveable into and out of the heat source. The reaction vessel has one or more sealing plugs, the positioning of which in relationship to the reaction vessel is controllable from a remote position. Also the one or more reaction vessel sealing plugs can include one or more conduits there through for delivery of reactants, gases at atmospheric or an elevated pressure, inert gases, drawing a vacuum and removal of reaction end products to and from the reaction vial, the reaction vial with sealing plug in position being operable at elevated pressures. The modular chemical production system is assembled from modules which can each include operating condition sensors and controllers configured for monitoring and controlling the individual modules and the assembled system from a remote position. Other modules include, but are not limited to a Reagent Storage and Delivery Module, a Cartridge Purification Module, a Microwave Reaction Module, an External QC/Analysis/Purification Interface Module, an Aliquotting Module, an F-18 Drying Module, a Concentration Module, a Radiation Counting Module, and a Capillary Reactor Module.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗