Background
Co‐morbid Alzheimer’s disease (AD) pathology in the form of amyloid‐β plaques and tau neurofibrillary tangles are frequently observed in people with probable dementia with Lewy bodies ...(DLB). Neurite Orientation Dispersion and Density Imaging (NODDI) is an emerging technique to characterize white matter (WM) tissue microstructure, although NODDI alterations and associations with AD biomarkers remain undefined in DLB. The objectives of this study are to compare NODDI and DTI parameters between DLB and controls and (ii) evaluate the pattern of DTI and NODDI changes associated with amyloid and tau deposition.
Method
Consecutive patients within the DLB spectrum (n = 45), including probable DLB (n = 32) and probable Mild Cognitive Impairment with Lewy bodies (MCI‐LB) (n = 13) from the Mayo Clinic ADRC underwent multi‐shell diffusion MRI, 18F‐Flortaucipir and 11C‐PiB PET. A comparison group of 45 age‐ and gender‐matched clinically unimpaired controls (CU) was included. Voxelwise non‐parametric permutation models were used to determine pair‐wise group differences and assess the associations of AD biomarkers with fractional anisotropy (FA), mean diffusivity (MD), tissue‐weighted neurite density index (tNDI; NDI x (1 – Free water fraction)) and orientation dispersion index (ODI), controlling for age. Complementary analyses were performed using regions‐of‐interest (ROI) obtained from the JHU atlas.
Result
Compared to CU, the DLB spectrum group exhibited widespread decreases in FA and tNDI and increases in MD and ODI, with the most pronounced effects in the cingulum bundles, uncinate, inferior and superior longitudinal fasciculi (Fig. 1). Greater 18F‐Flortaucipir uptake was also associated with lower FA and tNDI, and higher MD and ODI in the DLB spectrum compared to CU, independently of age and 11C‐PiB uptake (Fig. 2). In contrast, no associations were found between 11C‐PiB uptake and any of the DTI or NODDI parameters. Complementary ROI analyses corroborated these findings.
Conclusion
Widespread loss of WM integrity was observed on DTI and NODDI in probable DLB and prodromal DLB. These findings were associated with greater cortical tau, but not with amyloid‐β deposition. Although alpha‐synuclein pathology underlies the loss of WM integrity in DLB, amyloid‐independent tau pathology may also be an important influence on white matter integrity within the DLB spectrum.
Background
Co‐morbid Alzheimer’s disease (AD) pathology in the form of amyloid‐ß plaques and tau neurofibrillary tangles are frequently observed in people with probable dementia with Lewy bodies ...(DLB). Neurite Orientation Dispersion and Density Imaging (NODDI) is an emerging technique to characterize white matter (WM) tissue microstructure, although NODDI alterations and associations with AD biomarkers remain undefined in DLB. The objectives of this study are to compare NODDI and DTI parameters between DLB and controls and (ii) evaluate the pattern of DTI and NODDI changes associated with amyloid and tau deposition.
Method
Consecutive patients within the DLB spectrum (n = 45), including probable DLB (n = 32) and probable Mild Cognitive Impairment with Lewy bodies (MCI‐LB) (n = 13) from the Mayo Clinic ADRC underwent multi‐shell diffusion MRI, 18F‐Flortaucipir and 11C‐PiB PET. A comparison group of 45 age‐ and gender‐matched clinically unimpaired controls (CU) was included. Voxelwise non‐parametric permutation models were used to determine pair‐wise group differences and assess the associations of AD biomarkers with fractional anisotropy (FA), mean diffusivity (MD), tissue‐weighted neurite density index (tNDI; NDI x (1 – Free water fraction)) and orientation dispersion index (ODI), controlling for age. Complementary analyses were performed using regions‐of‐interest (ROI) obtained from the JHU atlas.
Result
Compared to CU, the DLB spectrum group exhibited widespread decreases in FA and tNDI and increases in MD and ODI, with the most pronounced effects in the cingulum bundles, uncinate, inferior and superior longitudinal fasciculi (Fig. 1). Greater 18F‐Flortaucipir uptake was also associated with lower FA and tNDI, and higher MD and ODI in the DLB spectrum compared to CU, independently of age and 11C‐PiB uptake (Fig. 2). In contrast, no associations were found between 11C‐PiB uptake and any of the DTI or NODDI parameters. Complementary ROI analyses corroborated these findings.
Conclusion
Widespread loss of WM integrity was observed on DTI and NODDI in probable DLB and prodromal DLB. These findings were associated with greater cortical tau, but not with amyloid‐ß deposition. Although alpha‐synuclein pathology underlies the loss of WM integrity in DLB, amyloid‐independent tau pathology may also be an important influence on white matter integrity within the DLB spectrum.
The chemical composition and properties of environmental media determine nanomaterial (NM) transport, fate, biouptake, and organism response. To compare and interpret experimental data, it is ...essential that sufficient context be provided for describing the physical and chemical characteristics of the setting in which a nanomaterial may be present. While the nanomaterial environmental, health and safety (NanoEHS) field has begun harmonization to allow data comparison and re-use (
e.g.
using standardized materials, defining a minimum set of required material characterizations), there is limited guidance for standardizing test media. Since most of the NM properties driving environmental behaviour and toxicity are medium-dependent, harmonization of media is critical. A workshop in March 2016 at Duke University identified five categories of test media: aquatic testing media, soil and sediment testing media, biological testing media, engineered systems testing media and product matrix testing media. For each category of test media, a minimum set of medium characteristics to report in all NM tests is recommended. Definitions and detail level of the recommendations for specific standardized media vary across these media categories. This reflects the variation in the maturity of their use as a test medium and associated measurement techniques, variation in utility and relevance of standardizing medium properties, ability to simplify standardizing reporting requirements, and in the availability of established standard reference media. Adoption of these media harmonization recommendations will facilitate the generation of integrated comparable datasets on NM fate and effects. This will in turn allow testing of the predictive utility of functional assay measurements on NMs in relevant media, support investigation of first principles approaches to understand behavioral mechanisms, and support categorization strategies to guide research, commercial development, and policy.
The chemical composition and properties of environmental media determine nanomaterial (NM) transport, fate, biouptake, and organism response.
Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite ...Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-β with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-β, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-β exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.
The effects of engineered natural organic amendments on the biodegradation and distribution of pyrene in soils were assessed. Pyrene was aged for 105 days in soils amended with either raw or ...superheated water (SHW)-processed MI peat or soybean stalks, and then subjected to biodegradation with specifically selected microorganisms for 130 days. Initial rates of pyrene mineralization in the soils were increased by addition of raw MI peat, but markedly decreased by additions of SHW-processed MI peat and both processed and raw soybean stalks. Pyrene sorbed by the processed organic sorbents was, however, slowly but steadily degraded by microorganisms over a greater than 4-month test period. Pyrene distributions in the soils were examined by sequential extractions of samples before and after biodegradation. Fractions of pyrene extracted readily with water or water/methanol mixtures were decreased substantially in both soils by the addition of processed amendments, while the nonextractable fractions associated with humic and fulvic acids and humin were increased markedly. The results demonstrate that SHW-processed amendments effectively reduce the ecological and human availability and aqueous phase extractability of organic contaminants while facilitating their steady microbial degradation and eventually complete remediation.
University of Michigan, Horace H. Rackham School of Graduate Studies
Carbon nanotubes comprise a class of nanomaterials having demonstrated promise for broad ranges of potential applications. The ...ecological and human health risks these nanomaterials may pose after release into environmental systems, however, are yet largely unknown.The lack of an adequate method for quantifying carbon nanotubes in environmental media has been a principal challenge associated with determining their environmental behaviors. To address this problem, a modified chemical vapor deposition process employing carbon-14 labeled methane was used to synthesize radioactively labeled single- and multi-walled carbon nanotubes (SWNTs and MWNTs). These nanotubes were used to show that HeLa cells rapidly and apparently irreversibly assimilated unmodified MWNTs. Given these results, previous qualitative detections of nanotubes in ecological receptors, and shared chemical properties with polycyclic aromatic hydrocarbons (PAHs), the bioaccumulation potential of nanotubes was investigated. The labeled nanotubes and a representative PAH, pyrene, were individually spiked to identical sediment and soil samples. The uptake and depuration behaviors of these compounds by the earthworm Eisenia foetida and the oligochaete Lumbriculus variegatus, potential entry points to terrestrial and aquatic food chains, were then assessed. Bioaccumulation values determined for the nanotubes were almost two orders of magnitude smaller than those measured for pyrene, indicating that purified nanotubes, unlike pyrene, are not readily absorbed into organisms.Carbon nanotubes are also commonly physically and chemically altered, and these modifications can change their physicochemical properties and possibly also their environmental behaviors. Purified MWNTs were treated with a 3:1 mixture of sulfuric to nitric acid, a process that made the nanotubes more hydrophilic. These nanotubes were similarly spiked to soils and sediments, but their ecological uptake was determined to be the same as that for the unmodified nanotubes.The octanol-water distribution coefficient, kow, represents a chemical property known to relate to bioaccumulation and is frequently employed for predictions thereof. A modified shake-flask method was used to measure the distributions of purified and 3:1 acid modified MWNTs between water and octanol. While their bioaccumulation behaviors were similar, different distribution coefficients were found for these nanotubes thus suggesting that, unlike typical hydrophobic organic chemicals, kow coefficients may not predict such behaviors for nanotubes.
PDF
